title: Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamic trial.
abstract: BACKGROUND
  Relaxin is upregulated in human heart failure (HF). Animal and clinical data suggest beneficial hemodynamic and renal effects from vasodilation. We determined safety, tolerability, and pharmacodynamic effects of human Relaxin in stable HF.
  
  
  RESULTS
  Sixteen patients were treated with open-label intravenous Relaxin in 3 dose-escalation cohorts and monitored hemodynamically for 24-hour infusion and postinfusion periods and followed until Day 30. The safety demonstrated in Group A (8-hour sequential infusions at dose levels of 10, then 30, and then 100 microg x kg x day equivalents) allowed escalation to Group B (240, 480, and 960 microg x kg x day). The highest safe dose, 960 microg x kg x day, was selected for a 24-hour infusion in Group C. Relaxin showed no adverse effects; produced hemodynamic effects consistent with vasodilation (ie, trends toward increases in cardiac index, decreases in pulmonary wedge pressure, and decreases in circulating NT-pro BNP without inducing hypotension; improved markers of renal function [creatinine, blood urea nitrogen]). The highest dose caused a transient elevation in creatinine and blood urea nitrogen at Day 9 that was without apparent clinical significance.
  
  
  CONCLUSIONS
  Relaxin was safe and well-tolerated in patients with stable HF, and preliminary pharmacodynamic responses suggest it causes vasodilation. Further evaluation of the safety and efficacy of this drug in HF appears warranted.
authors.affiliation: Department of Cardiology and Angiology, Charité - University Medicine Berlin, Campus Mitte, Germany. thomas.dschietzig@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Dschietzig
authors.forename: Sam
authors.initials: S
authors.lastname: Teichman
authors.forename: Elaine
authors.initials: E
authors.lastname: Unemori
authors.forename: Susy
authors.initials: S
authors.lastname: Wood
authors.forename: Julia
authors.initials: J
authors.lastname: Boehmer
authors.forename: Christoph
authors.initials: C
authors.lastname: Richter
authors.forename: Gert
authors.initials: G
authors.lastname: Baumann
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl