RATIONALE, DESIGN, AND ORGANIZATION OF THE METOPROLOL CR XL RANDOMIZED INTERVENTION TRIAL IN HEART-FAILURE (MERIT-HF)/

Metoprolol is a cardioselective beta blocker that has been shown to im prove left ventricular function and symptoms of congestive heart failu re (CHF) and also to decrease the number of hospitalizations due to CH F. However, the effects of metoprolol on mortality in patients with CH F have yet to be determined, Accordingly, the Metoprolol CR/XL Randomi zed intervention Trial in Heart Failure (MERIT-HF) has been designed t o investigate the effect of once-daily dosing of metoprolol succinate controlled release/extended release (CR/XL) when added to standard the rapy in patients with CHF. A total of 3,200 patients will be recruited for this international, double-blind, randomized, placebo-controlled survival study. The 2 primary objectives of MERIT-HF are to determine the effect of metoprolol CR/XL on (1) total mortality and (2) the comb ined endpoint of all-cause mortality and all-cause hospitalizations (t ime to first event). Eligible patients are 40-80 years old, with a red uced left ventricular ejection fraction (less than or equal to 0.40) a nd symptoms of CHF (New York Heart Association functional classes II-I V). After a 2-week placebo run-in period, an optimal allocation proced ure will be used to randomize patients in a 1:1 ratio to metoprolol CR /XL or matching placebo, After an initial titration phase starting wit h 12.5 mg or 25 mg once daily (depending on functional class), the tar get dose will be 200 mg in all patients who tolerate this dose. The me an follow-up is estimated to be 2.4 years, The study data will be anal yzed on an intention-to-treat basis. An Independent Safety Committee w ill monitor the safety aspects of the trial, and an Independent Endpoi nt Committee will classify all endpoints. (C) 1997 by Excerpta Medica, Inc.