Tezosentan in patients with acute heart failure: Design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS) - 21/08/11

Doi : 10.1016/j.ahj.2005.04.035

John R. Teerlink, MD ^a,^⁎ , John J.V. McMurray, MD ^b, Robert C. Bourge, MD ^c, John G.F. Cleland, MD ^d, Gadi Cotter, MD ^e, Guillaume Jondeau, MD ^f, Henry Krum, MD ^g, Marco Metra, MD ^h, Christopher M. O'Connor, MD ^e, John D. Parker, MD ⁱ, Guillermo Torre-Amione, MD, PhD ^j, Dirk J. Van Veldhuisen, MD ^k, Aline Frey, PharmD ^l, Maurizio Rainisio, PhD ^l, Isaac Kobrin, MD ^l
VERITAS Investigators
^a Section of Cardiology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, Calif
^b Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United Kingkom
^c Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala
^d Department of Cardiology, Castlehill Hospital, University of Hull, Kingston upon Hull, United Kingdom
^e Department of Medicine, Division of Cardiology, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC
^f Department of Cardiology, Hôpital Ambroise Paré, Boulogne, France
^g Departments of Medicine, Epidemiology and Preventive Medicine, Monash University Central and Eastern Clinical School, Alfred Hospital, Melbourne, Victoria, Australia
^h Department of Cardiology, University of Brescia, Brescia, Italy
ⁱ Mount Sinai and United Health Network Hospitals, Toronto, Canada
^j Methodist DeBakey Heart Center, The Winter's Center for Heart Failure Research, Baylor College of Medicine, Houston, Tex
^k Department of Cardiology, Thorax Center, University Hospital Groningen, Groningen, The Netherlands
^l Actelion Pharmaceuticals, Ltd, Allschwil, Switzerland

^⁎Reprint requests: John R. Teerlink, MD, Cardiology, 111C San Francisco VA Medical Center, 4150 Clement Street San Francisco, CA 94121-1545.

Résumé

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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