Acid-Base Composition With Use of hemoDialysates (ABChD)

Acid-Base Composition With Use of hemoDialysates: the ABChD Trial

This study is a prospective, single center, single blind (patient and laboratory), randomized, cross-over, two week investigation of intradialytic acid-base kinetics and physiology associated with use of two commercial acid dialysate concentrates in prevalent hemodialysis patients.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Device: Group 1: GranuFlo; Device: Group 2: NaturaLyte

Detailed Description

Approximately 10-20 prevalent hemodialysis patients will be recruited. Subjects will randomized to receive one weekly hemodialysis treatment using each of the two acetate acid dialysate buffers of NaturaLyte and GranuFlo, which will be assigned in a random fashion. Acetate and bicarbonate concentrations will be assessed before, at eight time points during, and six time points after the completion of hemodialysis.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group and New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects eligible to be entered into this study will meet all of the following criteria:

1. Adult female or male patients; age ≥18 years.
2. End stage renal disease (ESRD) patients treated for >90 days with the modality of maintenance hemodialysis and on a stable dialysis prescription for the prior month.
3. Patients utilizing a hemodialysis vascular access of a functioning arteriovenous fistula (AVF) or graft (AVG) during the prior month. The patient's AVF/AVG must be considered in stable functioning condition and not be expected to require any surgical revision/intervention during participation in the trial.
4. Patients with an average spKt/V of ≥1.2 during 30 days prior to screening as determined by historic monthly laboratory adequacy measurements; for patients with only one available spKt/V an average will not be performed. (Note: spKt/V should not be captured from dialysis machine adequacy measurements.)
5. Screening hemoglobin level of ≥9 g/dL, and investigator considers hemoglobin levels to have been clinically stable for at least 30 days.
6. A sodium bicarbonate basic dialysate prescription that has not had any changes for 30 days prior to randomization, and is anticipated to be unchanged during study participation as determined by the investigator.
7. Unchanged heparin dosing regimen for the past 30 days prior to randomization and anticipated unchanged heparin dosing during participation in this clinical trial.
8. No changes two weeks prior to randomization or anticipated changes throughout the study in any phosphate binders, calcium supplements, anticoagulant therapies that are not used for hemodialysis treatment (e.g. warfarin, dabigatran, apixaban, rivaroxaban and acetylsalicylic acid (ASA)), non-dialysate sodium bicarbonate and/or citrate based concomitant medications.
9. If treated with systemic glucocorticoid/corticosteroid medications, no dose changes in the previous two months before randomization, or anticipated dose changes throughout the study duration; the dosing regimen should be consistent with maintenance therapy (i.e. not for an acute or active uncontrolled disease) as determined by the investigator. (Note: this criteria does not pertain to inhaled and/or topical glucocorticoid/corticosteroid therapies)
10. During the two weeks prior to screening, an average of no more than 3.5 kg in pre-dialysis weight gain. In the event greater than 3.5 kg is noted, the investigator will discuss the specific medical history with the Medical Monitor prior to enrollment.
11. Willing to comply with all study procedures and be available for the duration of the study.

Exclusion Criteria:

Patients that meet any of the following criteria will be ineligible for this study:

1. Patients unable to provide a signed and dated informed consent for this clinical research study.
2. Pregnant or lactating female patients.
3. Females of reproductive potential who do not agree to use a highly effective method of contraception, as determined by the investigator.
4. Missed a scheduled outpatient dialysis treatment within two weeks prior to screening or anticipated to not attend any prescribed hemodialysis treatments during participation in the study.
5. Screening or historic laboratory values of aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels ≥ 2 times the upper limit of normal. These blood laboratory tests must have been performed within 30 days prior to screening or prior to randomization.
6. A screening or historic laboratory value of total bilirubin >1.9 mg/dL that was collected within 30 days prior to screening or obtained before randomization.
7. Uncontrolled clinically significant blood pressure as determined by the investigator within 30 days prior to screening.
8. Active or recent bleeding disorder within the past 30 days.
9. Screening or historic platelet count <100,000 platelets per microliter (mcL) that was collected within 30 days prior to screening or before randomization.
10. Chronic supplemental oxygen use within 30 days prior to randomization.
11. Current active and significant chronic obstructive pulmonary disease (COPD) as determined by the investigator.
12. Significant residual renal function as determined by the investigator. If the amount of residual renal function is in doubt, a 24 hour urine will be collected during the clinic admission to confirm the creatinine clearance. Decisions will be made after the results have been obtained as to the inclusion of data for these subjects.
13. Active malignancy or a malignancy within the past five years, with exceptions for basal and squamous cell carcinoma.
14. Active and clinically uncontrolled autoimmune disease as determined by the investigator. Subjects with controlled autoimmune diseases must be considered to be clinically stable in the opinion of the investigator (e.g. subjects with systemic lupus erythematosus (SLE) and no recent flares are not excluded). The investigator will consult with the referring physician if it is necessary to confirm the stability of an autoimmune disease.
15. Diagnosed with human immunodeficiency virus (HIV).
16. Diagnosed with congestive heart failure (CHF) class III or IV as classified by the New York Heart Association (NYHA) (refer to Appendix A) within the past 60 days.
17. Planned or anticipated need for any surgical procedures during participation in the study.
18. Current or recent illicit drug use or alcohol abuse as determined by the investigator.
19. Subjects that have any significant medical condition as determined by the investigator, which make her/him ineligible for the study (e.g. clinically significant vomiting on dialysis which affects acid-base status).
20. Any condition as determined by the investigator that would place the subject at an increased risk, or preclude the subject's full compliance with the study procedures and visits.
21. Treatment with an investigational drug, device or intervention within 30 days prior to and during participation in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: GranuFlo; Study subjects will be randomized to undergo dialysis treatments using GranuFlo, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using acid dialysate concentrations of NaturaLyte for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.	Device: Group 1: GranuFlo; Study subjects will be randomized to undergo dialysis treatments using GranuFlo, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using NaturaLyte, a commercially available acid dialysate concentration for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.; Other Names: GranuFlo 45X
Active Comparator: Group 2: NaturaLyte; Study subjects will be randomized to undergo dialysis treatments using NaturaLyte, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using acid dialysate concentrations of GranuFlo for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.	Device: Group 2: NaturaLyte; Study subjects will be randomized to undergo dialysis treatments using NaturaLyte, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using GranuFlo, a commercially available acid dialysate concentration for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.; Other Names: NaturaLyte 45X

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peridialytic Arterialized Blood Bicarbonate Concentrations	Quantification of Peridialytic Arterialized Blood Bicarbonate Concentrations	Immediately prior to initiation of hemodialysis, and 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis and 15, 30, 45, 60, 75, and 90 minutes post hemodialysis
Peridialytic Venous Blood Bicarbonate Concentrations	Quantification of Peridialytic Venous Blood Bicarbonate Concentrations	25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis
Peridialytic Arterialized Blood Acetate Concentrations	Quantification of Peridialytic Arterialized Blood Acetate Concentrations	Immediately prior to initiation of hemodialysis, and 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis and 15, 30, 45, 60, 75, and 90 minutes post hemodialysis
Peridialytic Venous Blood Acetate Concentrations	Quantification of Peridialytic Venous Blood Acetate Concentrations	25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis

Collaborators and Investigators

• Sponsor: Fresenius Medical Care North America
• Investigators: Principal Investigator: William B Smith, MD, Volunteer Research Group and New Orleans Center for Clinical Research

Publications and helpful links

General Publications

• Smith WB, Gibson S, Newman GE, Hendon KS, Askelson M, Zhao J, Hantash J, Flanagan B, Larkin JW, Usvyat LA, Thadhani RI, Maddux FW. The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation. BMC Nephrol. 2017 Aug 29;18(1):273. doi: 10.1186/s12882-017-0683-6.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 8, 2015

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 18, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: ABChD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No