Win Ratio DIAMOND Clinical Trial

Win Ratio Diamond Clinical Trial – Overview

The phase 3 DIAMOND trial was sponsored by Vifor Pharma, Inc., in collaboration with Syneos Health, LLC, and was completed in late 2021.

Aim of DIAMOND Trial

This study aims to evaluate the effects of patiromer compared to placebo on serum K+ in HF patients. This study is a multi-national, multi-center, randomized withdrawal, double-blind, placebo-controlled, parallel-group study. It includes screening and around 12 weeks of the Run-in Phase. Subjects have patiromer-initiated and RAASi medications and a randomized withdrawal, Blinded Treatment Phase.

The study participants include subjects suffering from heart failure (HF) with reduced ejection fraction (HFrEF) who are also experiencing hyperkalemia (elevated serum potassium K+) while receiving treatment with renin-angiotensin-aldosterone system inhibitor (RAASi) medications.

The study also includes participants who are normokalemic but have a history of hyperkalemia prior to screening, which necessitated significant adjustments to their RAASi medication.

Participants undergo a Run-in Phase lasting up to 12 weeks, followed by a Treatment Phase, the duration of which varies for each participant. Therefore, every participant’s study duration also varies, depending on their enrolment date.

Study Design

Study type – Interventional (clinical trial)

Actual enrolment – 878 participants

Allocation – Randomized

Interventional model – Parallel Assignment

Masking – Quadruple (Participant, Investigator, Care Provider, Outcomes Assessor)

Primary aim – Intervention

Outcome Measures

The primary outcome measure was the mean change from baseline in serum K+ levels. The secondary outcome measures involved time to the first event of hyperkalemia with a serum K+ value >5.5 mEq/L.

The outcome measured the duration participants could maintain the target MRA dose of 50 mg daily without a dose reduction below the target. The investigator reported adverse events of hyperkalemia. Hyperkalemia-related outcomes were evaluated using the Win Ratio method, prioritizing outcomes in the following hierarchical order:

1. Time to CV (cardiovascular) death
2. Number of CV hospitalizations overall
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

The RAASi use score was assessed using the Win Ratio method, incorporating additional factors such as:

1. All-cause of death
2. Occurrence of a CV hospitalization
3. HF medications use and dose for an ACEi/ARB/ARNi, and MRA, along with a beta-blocker

Every participant in each comparison is to have 0 to 8 points, and all participants are compared using this score at the right follow-up point in time.

Eligibility Criteria

The eligibility criteria for this clinical study require participants to be:

• At least 18 years or more of age
• Receive a dose of beta-blocker for treating HF
• Symptomatic low ejection fraction heart failure (weak heart muscle)
• Participants must have kidney function that is no worse than moderately impaired
• Participants must have high blood potassium levels (>5.0 mEq/L) and be receiving medication for heart failure
• Hospitalization for heart failure or treatment in an outpatient setting with intravenous medications within at least 12 months before screening
• Exclusion of subjects with current acute decompensated HF within four weeks prior to screening
• Exclusion of subjects who were hospitalized for acute decompensated HF within four weeks prior to screening
• Noticeable primary mitral valvular or aortic heart disease
• Heart transplantation or planned heart transplantation

Conclusion

This study is conducted at numerous locations worldwide, not limited to the United States. This phase 3 trial has been completed, and its main results (published in 2022) showed that patiromer significantly lowered the risk of recurrent hyperkalemia and helped patients maintain optimal RAAS inhibitor therapy, without any increase in adverse events.

To find more details about the Win Ratio Diamond clinical trial, you can access the official entry at https://www.clinicaltrials.gov/study/NCT03888066.

See Also

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Microdosing Mushroom Clinical Trials

Covance Clinical Trials

Randomized Clinical Trials

ICON Clinical Trials