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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
Results First Posted : February 24, 2023
Last Update Posted : February 24, 2023
Sponsor:
Collaborator:
Syneos Health, LLC
Information provided by (Responsible Party):
Vifor Pharma ( Vifor Pharma, Inc. )

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

Condition or disease Intervention/treatment Phase
Hyperkalemia Drug: Patiromer Drug: Placebos Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1195 participants
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
Official Title: 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)
Actual Study Start Date : April 24, 2019
Actual Primary Completion Date : September 2, 2021
Actual Study Completion Date : September 2, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
Drug Information available for: Patiromer

Arms and Interventions
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Arm Intervention/treatment
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.
 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
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.
 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).


Outcome Measures
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Primary Outcome Measures :
  1. Changes in Serum K+ Levels From Baseline [ Time Frame: 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 :
  1. CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time [ Time Frame: 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


  2. CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time [ Time Frame: 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


  3. Investigator-reported Events of Hyperkalemia [ Time Frame: 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.


  4. Hyperkalemia-related Hard Outcomes Endpoints [ Time Frame: 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


  5. RAASi Use Score [ Time Frame: 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.



Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03888066


Locations
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Sponsors and Collaborators
Vifor Pharma, Inc.
Syneos Health, LLC
Investigators
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Study Director: Peter Szecsödy, MD Vifor Pharma
  Study Documents (Full-Text)

Documents provided by Vifor Pharma ( Vifor Pharma, Inc. ):
Study Protocol  [PDF] June 23, 2021
Statistical Analysis Plan  [PDF] November 24, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Vifor Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03888066    
Other Study ID Numbers: PAT-CR-302
2018-005030-38 ( EudraCT Number )
First Posted: March 25, 2019    Key Record Dates
Results First Posted: February 24, 2023
Last Update Posted: February 24, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
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
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vifor Pharma ( Vifor Pharma, Inc. ):
treatment of hyperkalemia
chronic kidney disease
hypertension
hyperkalemia
potassium
spironolactone
 heart failure
Renin Angiotensin-Aldosterone System Inhibitor (RAASi)
RAASi
high potassium
eplerenone
reduced ejection fraction
Additional relevant MeSH terms:
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Heart Failure
Hyperkalemia
Heart Diseases
 Cardiovascular Diseases
Water-Electrolyte Imbalance
Metabolic Diseases