Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND)

Phase 3

Completed

Conditions: Hyperkalemia

Interventions: Drug: Placebos
Drug: Patiromer

Registration Number: NCT03888066

Lead Sponsor: Vifor Pharma, Inc.

Brief Summary: The purpose of this study is to assess the effects of patiromer compared with placebo on serum K+ in HF patients.

Detailed Description: Prospective Phase 3b multinational, multicenter, double-blind, placebo-controlled, randomized withdrawal, parallel group study that includes screening and up to 12 weeks Run-in Phase (all subjects will have patiromer initiated and RAASi medications, including mineralocorticoid receptor antagonist (MRA) optimized) and a randomized withdrawal Blinded Treatment Phase.

The study population includes subjects with heart failure (HF) with reduced ejection fraction (HFrEF) who are hyperkalemic (serum potassium \[K+\] \> 5.0 mEq/L) while receiving treatment with renin angiotensin aldosterone system inhibitor (RAASi) medications or who are normokalemic (serum K+ 4.0 - 5.0 mEq/L) but have a history of hyperkalemia prior to screening with subsequent reduction or discontinuation of a RAASi medication.

Each subject's participation includes a Run-in Phase (maximum 12 weeks) followed by the Treatment Phase (variable per subject). Study duration for individual subjects will vary, depending on their individual enrollment date. Subjects who prematurely discontinue patiromer/placebo will remain in the study for the collection of clinical events data and will receive usual care.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1195

Inclusion Criteria

Age at least 18 years or greater
Symptomatic low ejection fraction heart failure (weak heart muscle)
Receiving any dose of a beta blocker for the treatment of HF (unless not able to tolerate)
Kidney function not more than mild or moderately impaired
High blood potassium (>5.0 mEq/L) currently while receiving medications for heart failure OR normal blood potassium currently but previously had high potassium in the12 months prior to screening which caused a permanent reduction or discontinuation of heart failure medications
Hospitalization for heart failure or treatment in an out patient setting with intravenous medications within the last 12 months before screening.

Exclusion Criteria

Current acute decompensated HF, within 4 weeks before screening. Subjects with a discharge from a hospitalization for acute decompensation of HF longer than 4 weeks before screening may be included
Significant primary aortic or mitral valvular heart disease (except secondary mitral regurgitation due to left ventricular dilatation)
Heart transplantation or planned heart transplantation (i.e., currently on a heart transplant waiting list) during the study period

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2: Placebo	Placebos	Subjects will be randomized to receive a daily dose of placebo with possible dose adjustments based on subsequent local serum potassium levels.
Group 1: Patiromer	Patiromer	Subjects will be randomized to receive a daily dose of patiromer with possible dose adjustments based on subsequent local serum potassium levels.

Primary Outcome Measures

Name	Time	Method
Changes in Serum K+ Levels From Baseline	Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo	Adjusted mean changes in serum K+ from Baseline.

Secondary Outcome Measures

Name	Time	Method
Hyperkalemia-related Hard Outcomes Endpoints	Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo	Analyzed using Win Ratio approach with the following hierarchical components: 1. Time to CV death 2. Total number of CV hospitalizations 3. Total number of hyperkalemia toxicity events with serum K+ \>6.5 mEq/l 4. Total number of hyperkalemia events with serum K+ \>6.0-6.5 mEq/l 5. Total number of hyperkalemia events with serum K+ \>5.0 mEq/l MHTE=More hyperkalemia toxicity events; MHE=More hyperkalemia events; CV=Cardiovascular
RAASi Use Score	Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo	RAASi use score (0 to 8 points) analyzed using the Win Ratio approach for each pair of participants with the following additive components: 1. All-cause death 2. Occurrence of a CV hospitalization 3. HF medication use and dose for i) an ACEi/ARB/ARNi, ii) a MRA, and iii) a beta-blocker Each participant in each comparison can have 0-8 points and all participants are compared using this score at the respective appropriate follow-up time point. RAASi=renin-angiotensin-aldosterone system inhibitor; ACEi=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; ARNi=angiotensin receptor/neprilysin inhibitor; MRA=mineralocorticoid receptor antagonist.
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time	From Day 1/Baseline to week 90	Cumulative incidence of the first event of hyperkalemia with a serum K+ value \>5.5 mEq/l taking death as competing and calculated as CIF Estimates (95% CI) over time. Aalen-Johansen estimators of the cumulative incidence function with death as a competing event. CIF = cumulative incidence function; mEq/l = Milliequivalents Per Liter
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time	From Day 1/Baseline to week 102	Cumulative incidence of the reduction of the MRA dose below target dose calculated as CIF Estimates (95% CI) over time. Note: The reduction below the MRA target dose must last for at least 14 days (orless if at the end of study) to confirm this endpoint. CIF = cumulative incidence function; mEq/l = Milliequivalents Per Liter
Investigator-reported Events of Hyperkalemia	Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo	Participant's follow-up is from the date of the first dose of randomized study medication up to the participant's end of study date or 24 Jun 2021, whichever comes first. Annualized event rate per 100 subject-years= The total number of events for all subjects in the treatment group divided by the total subject-years of follow-up in that treatment group multiplied by 100.

Trial Locations

Locations (415): Investigator Site 11-080
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Alexander City, Alabama, United States
Investigator Site 11-041
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Huntsville, Alabama, United States
Investigator Site 11-153
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Phoenix, Arizona, United States
Investigator Site 11-097
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Tucson, Arizona, United States
Investigator Site 11-052
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Bakersfield, California, United States
Investigator Site 11-174
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Fremont, California, United States
Investigator Site 11-136
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Fresno, California, United States
Investigator Site 11-102
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Huntington Beach, California, United States
Investigator Site 11-162
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La Jolla, California, United States
Investigator Site 11-048
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La Mesa, California, United States
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Investigator Site 11-080
🇺🇸Alexander City, Alabama, United States