title: A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure.
abstract: OBJECTIVE
  The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF).
  
  
  RESULTS
  This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg, systolic blood pressure (BP) ≥ 115 mmHg, and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m(2) to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: -2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: -5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns.
  
  
  CONCLUSIONS
  The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. ClinicalTrials.gov identifier NCT01543854.
authors.affiliation: Department of Heart Diseases, Medical University, Military Hospital, Weigla 5, 50-981 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Veselin
authors.initials: V
authors.lastname: Mitrovic
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ruda
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernandez
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Alexander
authors.initials: A
authors.lastname: Vishnevsky
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.forename: Olga
authors.initials: O
authors.lastname: Milo
authors.forename: Ute
authors.initials: U
authors.lastname: Laessing
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Marion
authors.initials: M
authors.lastname: Dahlke
authors.forename: Robert
authors.initials: R
authors.lastname: Zymlinski
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012065:Relaxin / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
keywords: Acute heart failure; Clinical trial; Haemodynamics; Serelaxin