Case 19: Data monitoring experience in the moxonidine congestive Heart Failure Trial

The MOXonidine CONgestive Heart Failure Trial was a randomized placebo-controlled trial designed to evaluate reliably the effects of moxonidine, a central sympathetic inhibitor, on mortality and major morbid events in patients with heart failure. The primary endpoint was all-cause mortality, and the trial was intended to follow around 4,500 patients for an average of around 2.5 years until 724 deaths had occurred. Within a few months of study starting, the Data Monitoring Board (DMB) observed an emerging trend of an excess of death on moxonidine compared with placebo. Ten months after the first patient was randomized the study was stopped based on 46 versus 25 deaths in 990 moxonidine and 943 placebo patients respectively, p = 0.01. The final published evidence had 54 versus 32 deaths, p = 0.012. This study illustrates the problems faced by a DMB, and subsequently the trial Executive Committee and sponsor, in deciding how to act in the face of an emerging (and agonizing) negative trend for mortality in a major international trial. The paper also points to the difficulty of publishing results of such negative trials.