Tezosentan in patients with acute heart failure and acute coronary syndromes: Design of the Randomized Intravenous Tezosentan Study (RITZ-4)

Background Endothelin-1 is the most potent known endogenous vasoconstrictor. It is released during ischemia, and elevated levels have been demonstrated in hypertension, myocardial infarction, and heart failure. Tezosentan is a dual endothelin receptor antagonist, and it has improved cardiac output and,reduced pulmonary and systemic vascular resistance in experimental animal models and in initial human acute decompensated heart failure studies. Methods The Randomized Intravenous TeZosentan (RITZ-4) study was a multicenter, randomized, double-blind, placebo-controlled trial of tezosentan in patients with acute heart failure associated with acute coronary syndrome. The estimated sample size was 200 patients. Patients with evidence of acute heart failure and acute coronary syndrome were eligible for the study. Eligible patients were randomly assigned to tezosentan or matching placebo. The primary end point was the composite of death, worsening heart failure, recurrent ischemia, and recurrent or new myocardial infarction, within 72 hours after the start of study drug treatment. Secondary end points included all-cause death and hospitalization at 30 days, and length of initial hospital stay. Results Enrollment was completed in February 2001, with 193 patients enrolled. Conclusions The RITZ-4 study evaluated an important population in which few data are available to guide medical management. RITZ-4 will provide valuable safety and efficacy data with the novel compound tezosentan in patients with acute heart failure and acute coronary syndrome.