Patiromer for the management of hyperkalaemia in patients receiving renin–angiotensin–aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial

AIMS: In patients with current or a history of hyperkalaemia, treatment with renin–angiotensin–aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K(+)) binder, may improve serum K(+) levels and adherence to RAASi. METHODS: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single‐blinded run‐in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run‐in phase will last up to 12 weeks, following which patients will undergo double‐blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K(+) from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K(+) value >5.5 mEq/L, durable enablement of MRA at target dose, investigator‐reported adverse events of hyperkalaemia, hyperkalaemia‐related clinical endpoints and an overall RAASi use score (using a 0–8‐point scale) comprising all‐cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. CONCLUSION: The DIAMOND trial is designed to determine if patiromer can favourably impact K(+) control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use.