Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

Experimenteel: Study drug administration: furosemide

Study participants will receive furosemide oral tablets to be taken twice daily. During study period 1 (first 6 weeks), the drug dose will be escalated every 2 weeks if safe, tolerated, and acceptable to the participant. During study period 2 (subsequent 12 weeks), participants will take the maximum tolerated dose from study period 1, received every 4 weeks if safe, tolerated, and acceptable to the participant.

Geneesmiddel: Furosemide (loop diuretic) Tablets

Open label dose escalation study of furosemide in people receiving maintenance hemodialysis. Participants will take furosemide oral tablets twice daily for 18 weeks. Doses will be titrated every 2 weeks for 6 weeks if safe, effective, tolerated, and accepted by the participant. First 2 weeks of the study: participants not taking oral furosemide at enrollment will take 80mg furosemide twice daily, those taking oral furosemide at enrollment will stay on their prescribed dose, and those taking another loop diuretic at enrollment will discontinue their prescription and take an equivalent oral furosemide dose. At week 4: dose escalation if tolerated (from 80mg to 120mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). At week 6: dose escalation if tolerated (from 120mg to 160mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). Final 12 weeks: all participants will take the maximum tolerated dose.

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 5

Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.

• Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
• Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.

The percentage of participants who have a defined increase in 24-urine volume from baseline to week 5 will be determined.

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 12

Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.

• Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
• Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.

The percentage of participants who have a defined increase in 24-urine volume from baseline to week 12 will be determined.

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 18

Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.

• Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
• Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.

The percentage of participants who have a defined increase in 24-urine volume from baseline to week 18 will be determined.

Percentage of Participants With A Serum Potassium <3.2 mEq/L at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 1.

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 2.

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 3.

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 4.

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 5.

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 6.

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 9.

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 13.

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 17.

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 1

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 1 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 2

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 2 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 3

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 3 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 4

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 4 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 5

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 5 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 6

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 6 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 7

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 7 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 8

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 8 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 9

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 9 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 10

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 10 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 11

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 11 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 12

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 12 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 13

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 13 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 14

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 14 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 15

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 15 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 16

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 16 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 17

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 17 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 18

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 18 will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 1

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 1. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 2

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 2. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 3

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 3. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 4

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 4. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 5

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 5. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 6

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 6. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 8

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 8. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 10

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 10. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 12

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 12. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 14

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 14. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 16

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 16. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 18

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 18. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 1

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 1. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 2

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 2. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 3

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 3. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 4

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 4. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 5

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 5. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 6

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 6. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 8

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 8. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 10

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 10. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 12

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 12. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 14

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 14. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 16

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 16. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 18

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 18. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 1

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 1. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 2

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 2. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 3

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 3. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 4

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 4. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 5

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 5. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 6

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 6. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 8

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 8. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 10

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 10. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 12

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 12. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 14

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 14. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 16

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 16. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 18

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 18. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 19

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 19. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.