A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: The US Ecadotril Pilot Safety Study

Objective To determine the short-term safety and tolerability of the additi on of ecadotril to conventional therapy in patients with mild to moderate h eart failure. Methods Fifty ambulatory patients, 18 to 75 years of age, with mild to mode rate heart failure, left ventricular election fraction less than or equal t o 35%, taking stable doses of angiotensin-converting enzyme inhibitor, diur etics, and optionally digoxin were enrolled in a randomized, double-blind, placebo-controlled dose-escalation study of ecadotril 50 to 400 mg twice da ily versus conventional therapy alone. Results No increases in deaths, serious adverse events, or dropouts from ad verse events were observed for the ecadotril group compared with placebo. T he serum measures of neurohormonal activation were highly variable. Changes in signs and symptoms of heart failure, New York Heart Association class, and patient self-assessment of symptoms were not observed with ecadotril th erapy; however, the study was not designed to detect differences in these p arameters. Conclusion In this small pilot study, ecadotril in doses of 50 to 400 mg tw ice daily was generally well-tolerated and without severe short-term advers e effects in patients with mild to moderate heart failure. Evaluation of th e clinical efficacy and long-term safety of ecadotril and other neutral end opeptidase inhibitors in patients with heart Failure requires further study .