The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of ESRD Patients With Hyperkalemia

The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of End Stage Renal Disease Patients With Hyperkalemia

The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of ESRD Patients With Hyperkalemia (potassium greater than 5 milliequivalents per liter) is a non-randomized, crossover study. This is an open-label, pilot clinical trial with 3 sequential phases of (a) 2 weeks of no intervention, (b) 12 weeks of Patiromer treatment, and (c) 6 weeks of no intervention. Treatment with Patiromer will be initiated at a dose of 8.4 grams, once daily and observed for a week, then uptitrated to 16.8 grams once daily. Eligible study subjects will collect stool samples and provide blood and urine samples.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; ESRD; Hyperkalemia
• Intervention / Treatment: Drug: Patiromer

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • DaVita K Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects on stable hemodialysis for more than 90 days.
• Age 18-85 years.
• Persistent hyperkalemia, defined as elevated serum potassium > 5.0 mEq/L in more than 2 occasions during the previous 3 months.

Exclusion Criteria:

• Use of pre- or probiotics during the past 2 months
• Use of antibiotics within the past 2 months, if the patient received a single course of antibiotic.
• Presence of chronic wound infection and osteomyelitis
• Inflammatory bowel disease, chronic diarrhea, current C. difficile infection
• Liver cirrhosis or chronic active hepatitis
• Treatment with immunosuppressive medications in the past 6 months or more than a week of treatment with prednisone > 10 mg in the last 3 months
• Anticipated kidney transplant within 9 months
• Expected survival < 9 months
• Pregnancy, anticipated pregnancy, or breastfeeding
• Incarceration
• Participation in another intervention study
• severe anemia defined as hemoglobin < 8.0 g/dl any time during the last 2 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patiromer; This arm is a 2 week observation period before the start of the Patiromer treatment phase, followed by a 12 week treatment phase, and 6 week no treatment observation phase. Pre-Treatment (Wk 1-2): Observational period. Baseline sample collection of blood and stool. No medication. Treatment (Wk 3-14): Participants will take 8.4 grams of Patiromer once daily for one week, during which serum potassium and gastrointestinal symptoms will be evaluated. If tolerated and in the absence of hypokalemia, the dose will be up-titrated to 16.8 grams once daily for the remaining 11 weeks. Blood and stool will be collected. Post-Treatment (Wk 15-20): Observational period. No medication. Blood and stool will be collected.

Drug: Patiromer; Patiromer will be orally self-administered by participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events of Participants Taking Patiromer in Lowering Serum Potassium Levels in End Stage Renal Disease (ESRD) Patients With Hyperkalemia Measured by Gastrointestinal Symptom Rating Scale (GSRS)	The Gastrointestinal Symptom Rating Scale was used to measures any potential side effects due to study medication. Survey was administered at Wk 1, Wk 8, Wk 14, and Wk 20. For symptoms (abdomen pain - diarrhea) a score of 0 indicates "no discomfort", 1 = "mild discomfort", 2=moderate, 3=severe; higher score means a worse outcome For stool form, 1=Well formed, 2=Semi formed, 3= Loose, 4= Liquid;higher score means a worse outcome For number of stools per day, 1= <1, 2=1 or 2, 3=3 or 4, 4=5 or 6,5= 7 or more; higher score means a worse outcome	Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment)
Serum Potassium Level Through 12 Weeks of Treatment	Blood was collected during Pre-Treatment week 2, Treatment Week 14, and Post-Treatment week 20	Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment)
Changes in Blood Chemistry During the Study		Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment)
Stool Electrolytes During the Study Phases		Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Plasma Metabolites Using p-Cresol of Hyperkalemic ESRD Patients Treated With Patiromer	Blood and stool samples collected from the ESRD patient will be collected at pre-specified time points and analyzed by untargeted and targeted metabolomics for stool and serum metabolome profiles.	Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment)
Changes in Gut Microbiome of Hyperkalemic ESRD Patients Treated With Patiromer.	Blood and stool samples collected from the ESRD patient will be collected at pre-specified time points and analyzed by metagenomics for gut microbiome profile.	Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-treatment)

Collaborators and Investigators

• Sponsor: Dominic Raj

Publications and helpful links

General Publications

• Amdur RL, Paul R, Barrows ED, Kincaid D, Muralidharan J, Nobakht E, Centron-Vinales P, Siddiqi M, Patel SS, Raj DS. The potassium regulator patiromer affects serum and stool electrolytes in patients receiving hemodialysis. Kidney Int. 2020 Nov;98(5):1331-1340. doi: 10.1016/j.kint.2020.06.042. Epub 2020 Aug 1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 26, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; ESRD; Hyperkalemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Water-Electrolyte Imbalance; Kidney Diseases; Kidney Failure, Chronic; Hyperkalemia
• Other Study ID Numbers: 071738

Drug and device information, study documents

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