Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS).
BACKGROUND
Endothelin 1 is a potent endogenous vasoconstrictor neurohormone, and endothelin 1 plasma concentrations predict adverse outcomes in patients with acute heart failure (AHF). Tezosentan, an intravenous endothelin receptor antagonist, improved hemodynamics in patients with AHF; however, its effects on morbidity and mortality have not been evaluated.


METHODS
The VERITAS program consists of 2 identical, double-blind, randomized, placebo-controlled, concurrently conducted trials (VERITAS-1 and VERITAS-2), performed in 150 centers in Europe, Israel, Australia, and North America. The program is designed to enroll at least 1760 patients hospitalized with dyspnea at rest because of AHF requiring intravenous therapy. In addition to conventional therapy, patients are randomized to receive tezosentan (5 mg/h for 30 minutes, then 1 mg/h for 24-72 hours) or matching placebo. The 2 prespecified primary end points are the incidence of death or worsening heart failure at 7 days in the combined studies and the change from baseline in dyspnea over the first 24 hours of treatment, measured using a visual analog scale in VERITAS-1 and VERITAS-2, individually.


RESULTS
Enrollment started in April 2003, and the program was discontinued in November 2005 because of the low probability of achieving a significant treatment effect.


CONCLUSIONS
No currently available agents have been shown in a prospective, randomized, clinical trial to improve outcomes in patients with AHF. Thus, the VERITAS program will provide valuable insights into the effect of tezosentan on clinical outcomes in patients with AHF, as well as hemodynamics and clinical symptoms.
Teerlink
John R
JR
San Francisco Veterans Affairs Medical Center, University of California, San Francisco, California, USA. johnt@itsa.ucsf.edu
McMurray
John J V
JJ
Bourge
Robert C
RC
Cleland
John G F
JG
Cotter
Gadi
G
Jondeau
Guillaume
G
Krum
Henry
H
Metra
Marco
M
O'Connor
Christopher M
CM
Parker
John D
JD
Torre-Amione
Guillermo
G
Van Veldhuisen
Dirk J
DJ
Frey
Aline
A
Rainisio
Maurizio
M
Kobrin
Isaac
I
D000208:Acute Disease; D000328:Adult; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan