RELAX TRIAL: Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial

RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 μg/kg per day)( vasoactive peptide hormone with many biological and haemodynamic effects) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat.1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm × h, 95% CI 120—775; p=0•007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0•70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13•0%]; serelaxin, 76 events [13•2%]; hazard ratio [HR] 1•02 [0•74—1•41], p=0•89] or days alive out of the hospital up to day 60 (placebo, 47•7 [SD 12•1] days; serelaxin, 48•3 [11•6]; p=0•37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0•63, 95% CI 0•42—0•93; p=0•019).

Interpretation:Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality.

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