Design of the RELAXin in acute heart failure study

Am Heart J. 2012 Feb;163(2):149-55.e1. doi: 10.1016/j.ahj.2011.10.009.

Abstract

Background: Acute heart failure (AHF) remains a major public health burden with a high prevalence and poor prognosis. Relaxin is a naturally occurring peptide hormone that increases cardiac output, arterial compliance, and renal blood flow during pregnancy. The RELAX-AHF-1 study will evaluate the effect of RLX030 (recombinant form of human relaxin 2) on symptom relief and clinical outcomes in patients with AHF.

Methods: The protocol includes a completed phase 2 234-patient dose-finding study (Pre-RELAX-AHF) and an ongoing phase 3 1,160-patient trial (RELAX-AHF-1). Patients with AHF and systolic blood pressure >125 mm Hg are randomized within 16 hours of presentation to a 48-hour IV infusion of RLX030 or placebo. The 30 μg/kg per day dose of RLX030 was chosen for RELAX-AHF-1 based on effects on dyspnea, clinical outcomes, and safety observed in Pre-RELAX-AHF. Primary efficacy end points in RELAX-AHF-1 are (1) the area under the curve of change of the dyspnea Visual Analog Scale from baseline through day 5 and (2) whether the patient reports moderately to markedly better dyspnea at 6, 12, and 24 hours. Secondary efficacy end points include days alive and out of the hospital through day 60 and cardiovascular death or rehospitalization for heart failure or renal failure through day 60. Patients will be followed up through day 180 for mortality. As of September 19, 2011, 978 patients have been enrolled.

Conclusions: Pre-RELAX-AHF results suggested that infusion of RLX030 may accelerate dyspnea relief and improve prognosis in patients hospitalized with AHF. RELAX-AHF-1 will further evaluate these effects.

Trial registration: ClinicalTrials.gov NCT00520806.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Infusions, Intravenous
  • Length of Stay
  • Male
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Relaxin / administration & dosage*
  • Stroke Volume / drug effects
  • Survival Rate / trends
  • Treatment Outcome
  • Vascular Resistance / drug effects

Substances

  • RLN2 protein, human
  • Recombinant Proteins
  • Relaxin

Associated data

  • ClinicalTrials.gov/NCT00520806