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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03888066
Recruitment Status : Completed
First Posted : March 25, 2019
Last Update Posted : October 21, 2021
Sponsor:
Information provided by (Responsible Party):
Vifor Pharma ( Vifor Pharma, Inc. )

Tracking Information
First Submitted Date  ICMJE March 12, 2019
First Posted Date  ICMJE March 25, 2019
Last Update Posted Date October 21, 2021
Actual Study Start Date  ICMJE April 25, 2019
Actual Primary Completion Date September 2, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2021)
Mean change from baseline in serum K+ levels. [ Time Frame: Day 1/baseline, through study completion (end of study visit) ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
Time to first occurrence of CV death or CV hospitalization (or equivalent in outpatient clinic) [ Time Frame: 6 months to 2.5 years ]
To determine if patiromer treatment of subjects who developed hyperkalemia while receiving RAASi medications will result in continued use of RAASi medications in accordance with heart failure (HF) treatment guidelines and thereby decrease the occurrence of the combined endpoint of cardiovascular (CV) death and CV hospitalization events compared with placebo treatment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2021)
  • Time to the first event of hyperkalemia with a serum K+ value >5.5 mEq/L. [ Time Frame: Day 1/baseline, through study completion (end of study visit) ]
  • Durable enablement to stay on the MRA target dose (of 50 mg daily spironolactone or eplerenone, respectively) [ Time Frame: Day 1/baseline, through study completion (end of study visit) ]
    The time to the event of reduction of the MRA dose below target
  • Investigator reported adverse events (AEs) of hyperkalemia. [ Time Frame: From screening, through study completion and up to 2 weeks after the end of study ]
  • Hyperkalemia-related hard outcomes endpoints [ Time Frame: Day 1/baseline, through study completion (end of study visit) ]
    Analyzed using Win Ratio approach with the following hierarchical components:
    1. Time to cardiovascular (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
  • RAASi Use Score [ Time Frame: Day 1/baseline, through study completion (end of study visit) ]
    Analyzed using the Win Ratio approach for each pair of subjects 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) an MRA, and iii) a beta-blocker
    Each subject in each comparison can have 0-8 points and all subjects are compared using this score at the respective appropriate follow-up time point.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Proportion of subjects on ≥ 50% of guideline-recommended target dose of RAASi medications [ Time Frame: Through End of Study Visit, approximately 2.5 years ]
    Proportion of subjects on ≥ 50% of guideline-recommended target dose of angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or ARNi and ≥ 50% of guideline-recommended target dose of MRA at the End of Study Visit
  • Total HF hospitalizations [ Time Frame: Through End of Study Visit, approximately 2.5 years ]
    Total HF hospitalizations (or equivalent in outpatient clinic)
  • Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Through End of Study Visit, approximately 2.5 years ]
    Patient reported outcome: Kansas City Cardiomyopathy Questionnaire (KCCQ)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND)
Official Title  ICMJE A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal, Parallel Group Study of Patiromer for the Management of Hyperkalemia in Subjects Receiving Renin Angiotensin Aldosterone System Inhibitor (RAASi) Medications for the Treatment of Heart Failure (DIAMOND)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective Phase 3b multinational, multicenter, double-blind, placebo-controlled, randomized withdrawal, parallel group study that includes screening and 12 weeks Run-in Phase and a randomized withdrawal Blinded Treatment Phase.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Hyperkalemia
Intervention  ICMJE
  • Drug: Patiromer
    The starting dose of patiromer will be 1 packet/day and may be taken either with food or without food. Based upon the patiromer treatment algorithm patiromer may be increased by 1 packet per day in intervals of at least 1 week (± 3 days). For subjects who become hypokalemic, patiromer may be decreased to a minimum of 0 packets/day. Doses of patiromer will be 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
    Other Name: Veltassa
  • Drug: Placebos
    The starting dose of placebo will be 1 packet/day and may be taken either with food or without food. Based upon the placebo treatment algorithm placebo may be increased by 1 packet per day in intervals of at least 1 week (± 3 days). For subjects who become hypokalemic, placebo may be decreased to a minimum of 0 packets/day. Doses of placebo will be 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
Study Arms  ICMJE
  • Experimental: Group 1: Patiromer
    Subjects will be randomized to receive a daily dose of patiromer with possible dose adjustments based on subsequent local serum potassium levels.
    Intervention: Drug: Patiromer
  • Placebo Comparator: Group 2: Placebo
    Subjects will be randomized to receive a daily dose of placebo with possible dose adjustments based on subsequent local serum potassium levels.
    Intervention: Drug: Placebos
Publications * Bolaños JA, Seliger SL. Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Treatment: Stuck between a Rock and a Hard Place. Clin J Am Soc Nephrol. 2021 Mar 8;16(3):345-347. doi: 10.2215/CJN.00950121. Epub 2021 Feb 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2021)
878
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2019)
2388
Actual Study Completion Date  ICMJE September 2, 2021
Actual Primary Completion Date September 2, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Brazil,   Bulgaria,   Canada,   Czechia,   France,   Georgia,   Germany,   Hungary,   Israel,   Italy,   Mexico,   Netherlands,   Poland,   Russian Federation,   Serbia,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03888066
Other Study ID Numbers  ICMJE PAT-CR-302
2018-005030-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame:

Data can be requested 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later.

Data will be indefinitely available for requesting

Access Criteria: A research proposal must be approved by an independent review panel and the study sponsor and researchers must sign a data sharing agreement.
Responsible Party Vifor Pharma ( Vifor Pharma, Inc. )
Study Sponsor  ICMJE Vifor Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Peter Szecsödy, MD Vifor Pharma
PRS Account Vifor Pharma
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP