Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients

Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients Treated With Hemodialysis (PEARL-HD)

The purpose of this study is to determine whether once-daily dosing of patiromer will reduce the frequency of hyperkalemic episodes in ESRD (end stage renal disease) study participants who receive conventional hemodialysis (HD). The study objective is to determine if patiromer administered orally once a day with breakfast or lunch will reduce episodes of hyperkalemia in ESRD study participants who receive thrice-weekly HD.

Study Overview

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

Detailed Description

This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice weekly HD schedule will be screened from retrospective review of clinical and laboratory parameters from our clinical practice group. A total of 40 study participants (randomized 1:1 study drug: usual care) will be enrolled. Duration of study medication exposure will be 4 weeks. The total duration of study, from enrollment until the end of the washout period will be 7 weeks.

This is a proof of concept study, to determine whether administration of patiromer has the potential to change the risk category for ESRD patients who are on conventional HD schedules. In addition, the study will develop and pilot study procedures that could be implemented in a large-scale clinical trial. By nature of the limited size of the study, the power of the trial will be limited. Reducing serum potassium with the use of low dialysate potassium is actually associated with an increased risk of sudden cardiac death. Furthermore, HD patients already carry a high pill burden, and it is unclear if prescription of an additional oral medication will reduce the frequency of episodic hyperkalemia.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • DaVita Dialysis Sites

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and Females, age at least 18 years
• ESRD treated with thrice-weekly HD for ≥ 6 months.
• At least two measured pre-dialysis serum [K] ≥ 5.5 mEq/L or one [K] ≥ 6.0 mEq/L noted over the past three months
• Current use of dialysate with potassium concentration ≤ 2 mEq/L
• Typical consumption of at least two meals per day
• Have received customary dietary instruction over prior month
• Considered by the treating physician(s) to be in otherwise stable clinical condition.
• If patient is of childbearing potential, he/she will be willing to avoid pregnancy during the study using an acceptable birth control method.

Exclusion Criteria:

• Not considered by the treating physician(s) to be adherent with recommended dialysis schedule and prescribed medications
• Life expectancy < 3 months
• Dialysis-dependent for less than 6 months
• Non-elective hospitalization in prior 3 months
• Currently prescription of oral potassium supplements
• In the prior 3 months, therapy with oral potassium-lowering medication
• Underlying severe gastrointestinal disorders, including history of ischemic bowel.
• Corrected serum calcium concentration > 10.5 mg/dL in prior three months
• Anticipated kidney transplant within the next 3 months
• Prisoners or others who are involuntarily incarcerated or detained
• Pregnant, breastfeeding, or considering pregnancy.
• Participation in a clinical trial of an experimental treatment within the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patiromer Oral Powder Product; Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L.	Drug: Patiromer Oral Powder Product; Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L. Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol; Other Names: Valtressa
No Intervention: Usual care arm; Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Episodes of Serum Potassium ≥ 5.5 mEq/L	To determine if patiromer administered orally once a day with the mid-day meal will reduce episodes of hyperkalemia in ESRD patients who receive thrice-weekly HemoDiaylsis.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant	To determine if patiromer administered orally once a day with the mid-day meal will reduce episodes of hyperkalemia in ESRD patients who receive thrice-weekly HemoDiaylsis.	4 weeks
Median Daily Dose of Patiromer That Was Given in Treatment Arm		Week 3
Number of Additional Hemodialysis Treatments Due to Hyperkalemia	To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia	4 weeks
Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline	Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but < 30 seconds), > 3 second pause), atrial fibrillation (> 30 seconds), premature ventricular contractions > 500/24h or bradycardia (heart rate < 40 for 5 consecutive beats).	Baseline
Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4	Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but < 30 seconds), > 3 second pause), atrial fibrillation (> 30 seconds), premature ventricular contractions > 500/24h or bradycardia (heart rate < 40 for 5 consecutive beats).	Week 4
Number of Participants Who Completed All Study Visits	To determine feasibility of a large-scale hemodialysis-based trial.	4 weeks
Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours	PVCs are irregular contractions that start in the ventricles instead of the atria.	4 weeks
Change in Serum Albumin Concentration	To determine the between-group differences in serum albumin concentrations.	4 weeks
Change in Parathyroid Hormone (PTH) Concentration	To determine the between-group differences in PTH concentrations.	4 weeks
Change in Serum Potassium Concentration Two Weeks After Study Drug is Discontinued	To determine the change in serum potassium concentration two weeks after study drug is discontinued	6 weeks
Change in Serum Phosphorus Concentration Two Weeks After Study Drug Has Been Discontinued	To determine the change in serum phosphorus concentration two weeks after study drug has been discontinued	6 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Vifor Pharma
• Investigators: Principal Investigator: John P Middleton, MD, Duke University

Publications and helpful links

General Publications

• Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Hemodialysis
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Water-Electrolyte Imbalance; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Hyperkalemia
• Other Study ID Numbers: Pro00088688

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant level data will not be shared.

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