Tezosentan in patients with acute heart failure: design of the Value of
Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study
(VERITAS).
Author(s): Teerlink JR(1), McMurray JJ, Bourge RC, Cleland JG, Cotter G, Jondeau G, Krum H,
Metra M, O'Connor CM, Parker JD, Torre-Amione G, Van Veldhuisen DJ, Frey A,
Rainisio M, Kobrin I; VERITAS Investigators.
Affiliation(s): Author information:
(1)San Francisco Veterans Affairs Medical Center, University of California, San
Francisco, California, USA. johnt@itsa.ucsf.edu
Publication date & source: 2005, Am Heart J. , 150(1):46-53
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.
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