Evaluation of Patiromer in Heart Failure Patients (PEARL-HF)

A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of Patiromer in Heart Failure Patients

The purpose of this study was to assess the effects of patiromer on serum potassium participants with heart failure. This study also assessed the safety and tolerability of patiromer in participants with heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Hyperkalemia
• Intervention / Treatment: Drug: placebo; Drug: patiromer

Detailed Description

This was a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study in congestive heart failure participants. Depending on the outcome from the initial cohort of 100 participants (Part 1), a second cohort of 170 participants could have been enrolled (Part 2). Based on the results of Part 1 of the study, Part 2 was not conducted.

Participants were randomly assigned to and received patiromer (30 g/day) or placebo for up to 28 days. All participants also received spironolactone; the initial spironolactone dose was 25 mg daily and was increased to 50 mg daily for participants who had a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits occurred on treatment Days 3, 7, 14, 17, 21 and 28. A safety follow-up contact was made 7 days after administration of last dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 62500
    • Investigator Site 102
  • Prague, Czechia, 12008
    • Investigator site 104
  • Prague, Czechia, 14021
    • Investigator Site 103
• Georgia
  • Tbilisi, Georgia, 0102
    • Investigator Site 605
  • Tbilisi, Georgia, 0159
    • Investigator Site 602
  • Tbilisi, Georgia, 0164
    • Investigator Site 604
  • Tbilisi, Georgia, 0179
    • Investigator Site 603
• Germany
  • Gottingen, Germany, 37075
    • Investigator site 201
  • Heidelberg, Germany, 69120
    • Investigator site 202
• Poland
  • Warsaw, Poland, 02637
    • Investigator Site 305
• Russian Federation
  • Barnaul, Russian Federation, 656099
    • Investigator Site 409
  • Kemerovo, Russian Federation, 650002
    • Investigator Site 407
  • Moscow, Russian Federation, 111020
    • Investigator Site 406
  • Moscow, Russian Federation, 111539
    • Investigator Site 402
  • Moscow, Russian Federation, 129301
    • Investigator Site 403
  • St Petersburg, Russian Federation, 197341
    • Investigator Site 404
  • St Petersburg, Russian Federation, 198205
    • Investigator Site 412
  • St Petersburg, Russian Federation, 199106
    • Investigator Site 405
• Ukraine
  • Dnipropetrovsk, Ukraine, 49023
    • Investigator Site 507
  • Kharkiv, Ukraine, 61018
    • Investigator Site 502
  • Kharkiv, Ukraine, 61176
    • Investigator Site 509
  • Kiev, Ukraine, 03680
    • Investigator Site 504
  • Kiev, Ukraine, 03680
    • Investigator Site 506
  • Kiev, Ukraine, 04114
    • Investigator Site 501
• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Investigator Site 029
    • Port Charlotte, Florida, United States, 33952
      • Investigator Site 031
  • Illinois
    • Peoria, Illinois, United States, 61606
      • Investigator Site 009
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Investigator Site 018
  • New York
    • Buffalo, New York, United States, 14215
      • Investigator Site 020
    • Northport, New York, United States, 11768
      • Investigator Site 005
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Investigator Site 022
  • Texas
    • Dallas, Texas, United States, 75216
      • Investigator Site 001
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Investigator Site 019

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:

• Participants with chronic heart failure clinically indicated to receive spironolactone therapy, aged 18 years or older with serum potassium level of 4.3 - 5.1 mEq/L at screening and baseline, AND (1) chronic kidney disease (GFR < 60 mL/min) OR (2) documented history of hyperkalemia within the last 6 months
• Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion
• Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion
• Must sign informed consent document

Exclusion Criteria:

• History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
• Uncorrected hemodynamically significant primary valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia
• Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation
• Heart transplant recipient, or anticipated need for transplant during study participation
• Any of the following events having occurred within 3 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke
• Current dialysis participant, or anticipated need for dialysis during study participation
• Prior kidney transplant, or anticipated need for transplant during study participation
• Metastatic, late-stage or end-stage cancer with < 12 months life expectancy
• History of alcoholism or drug/chemical abuse within 1 year
• QTcB interval > 500 msec (Bazett's correction formula)
• Sustained systolic blood pressure > 170 or < 90 mmHg
• Liver enzymes (ALT, AST) > 3 times upper limit of normal
• Use of oral cardiac medications (including loop and thiazide diuretics) that have not been stable for at least 21 days prior to baseline and are not anticipated to remain stable during study participation
• Use of any IV cardiac medications within 21 days prior to baseline, or their anticipated need during study participation.
• Current use of polymer-based drugs (e.g. Renagel, Kayexalate, Welchol, Colestid), other phosphate binders or potassium binders, calcium supplements, antacids (eg TUMS, Maalox), or their anticipated need during study participation
• Use of aldosterone antagonist in the last 30 days prior to baseline, unless was discontinued due to hyperkalemia
• Use of potassium sparing medication and/or potassium supplements in the last 30 days prior to baseline
• Use of any investigational medication, 30 days or 5 half-lives whichever is longer, prior to baseline
• Participants who have taken investigational product in this study, or a previous patiromer study
• Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol
• In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo
Active Comparator: patiromer	Drug: patiromer; Active investigational drug; Other Names: RLY5016; Veltassa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.	Baseline and Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.	Analysis based on central laboratory data.	28 Days
Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).	Analysis based on local laboratory data.	28 Days
Proportion of Participants Whose Spironolactone Dose Was Increased.		28 Days
Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L		Baseline and Day 28
Time to First Elevated Serum K+ > 5.5 mEq/L.		28 Days

Collaborators and Investigators

• Sponsor: Relypsa, Inc.
• Collaborators: Medpace, Inc.

Publications and helpful links

General Publications

• Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ; PEARL-HF Investigators. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011 Apr;32(7):820-8. doi: 10.1093/eurheartj/ehq502. Epub 2011 Jan 5.
• 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.

Helpful Links

• Relypsa company website

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 23, 2009
• First Submitted That Met QC Criteria: March 24, 2009
• First Posted (Estimate): March 25, 2009

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Heart failure; chronic kidney disease; HF; hyperkalemia; prevention of hyperkalemia in heart failure participants
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Water-Electrolyte Imbalance; Heart Failure; Hyperkalemia
• Other Study ID Numbers: RLY5016-202

Drug and device information, study documents

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