Clinical Trials

❘❙❚■ Chapter 1 | Randomized Clinical Trialsdeath from any cause in the total CHARM population [14]. In each componenttrial, the primary endpoint was the time to the first occurrence of cardiovasculardeath or emergency hospitalization for the management of CHF (accordingly, theprimary analysis of each component trial was based on this endpoint) [15–17].It was ethically acceptable to perform this trial since there was not enough evidenceto support the use of candesartan in patients with CHF prior to this study.The objectives and the endpoints were clearly stated in advance, and conclusionswith respect to the effect of candesartan were based on these prespecifiedobjectives and endpoints.Study designCHARM was a multicenter study consisting of three separate, two-arm,randomized, double-blinded, placebo-controlled subtrials into which patientswere allocated depending on their left ventricular ejection fraction (strength oftheir heart function) and background use of angiotensin-converting enzyme(ACE) inhibitors at presentation [14–17]. Patients who had preserved leftventricular function (left ventricular ejection fraction ≥40%) were randomlyallocated to either candesartan or placebo in the ‘CHARM-Preserved’ trial.Patients who had left ventricular ejection fraction