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.