Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many
biological and haemodynamic effects. In a pilot study, serelaxin was safe and well
tolerated with positive clinical outcome signals in patients with acute heart failure.
The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have
greater dyspnoea relief compared with patients treated with standard care and placebo.
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) 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.
This trial is registered at ClinicalTrials.gov, NCT00520806.
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).
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.
Corthera, a Novartis affiliate company.
Copyright © 2013 Elsevier Ltd. All rights reserved.