Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study

John R. Teerlink, Adriaan A. Voors, Piotr Ponikowski, Peter S. Pang, Barry H. Greenberg, Gerasimos Filippatos, G. Michael Felker, Beth A. Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A. Hua, Thomas Severin, Marco Metra

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180. RELAX-AHF-2 (ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX-AHF-2 is a multicentre, randomized, double-blind, placebo-controlled, event-driven, phase 3 trial enrolling ∼6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild-to-moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all-cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in-hospital length of stay during index AHF. The results from RELAX-AHF-2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF.

Original languageEnglish (US)
Pages (from-to)800-809
Number of pages10
JournalEuropean Journal of Heart Failure
Volume19
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • Acute heart failure
  • Mortality
  • Phase 3 trial
  • Serelaxin
  • Worsening heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Teerlink, J. R., Voors, A. A., Ponikowski, P., Pang, P. S., Greenberg, B. H., Filippatos, G., Felker, G. M., Davison, B. A., Cotter, G., Gimpelewicz, C., Boer-Martins, L., Wernsing, M., Hua, T. A., Severin, T., & Metra, M. (2017). Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study. European Journal of Heart Failure, 19(6), 800-809. https://doi.org/10.1002/ejhf.830