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 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

51 Citations (Scopus)

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)
JournalEuropean Journal of Heart Failure
DOIs
StateAccepted/In press - 2017

Fingerprint

Heart Failure
Therapeutics
Placebos
Mortality
Dyspnea
Renal Insufficiency
Length of Stay
Blood Pressure
Relaxin
Natriuretic Peptides
Standard of Care
Intravenous Infusions
Thorax
Hormones
Morbidity
Kidney
Pregnancy

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Serelaxin in addition to standard therapy in acute heart failure : Rationale and design of the RELAX-AHF-2 study. / Teerlink, John R.; Voors, Adriaan A.; Ponikowski, Piotr; Pang, Peter; Greenberg, Barry H.; Filippatos, Gerasimos; Felker, G. Michael; Davison, Beth A.; Cotter, Gad; Gimpelewicz, Claudio; Boer-Martins, Leandro; Wernsing, Margaret; Hua, Tsushung A.; Severin, Thomas; Metra, Marco.

In: European Journal of Heart Failure, 2017.

Research output: Contribution to journalArticle

Teerlink, JR, Voors, AA, Ponikowski, P, Pang, P, Greenberg, BH, Filippatos, G, Felker, GM, Davison, BA, Cotter, G, Gimpelewicz, C, Boer-Martins, L, Wernsing, M, Hua, TA, 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. https://doi.org/10.1002/ejhf.830
Teerlink, John R. ; Voors, Adriaan A. ; Ponikowski, Piotr ; Pang, Peter ; Greenberg, Barry H. ; Filippatos, Gerasimos ; Felker, G. Michael ; Davison, Beth A. ; Cotter, Gad ; Gimpelewicz, Claudio ; Boer-Martins, Leandro ; Wernsing, Margaret ; Hua, Tsushung A. ; Severin, Thomas ; Metra, Marco. / Serelaxin in addition to standard therapy in acute heart failure : Rationale and design of the RELAX-AHF-2 study. In: European Journal of Heart Failure. 2017.
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