Data monitoring in the Prospective Randomized Milrinone Survival Evaluation: Dealing with an agonizing trend

The Prospective Randomized Milrinone Survival Evaluation (PROMISE) was conducted to clarify discordant findings in previous experimental and clinical studies with milrinone, a cyclic AMP-enhancing positive inotropic agent. Earlier studies had shown positive effects of milrinone on cardiac function and exercise performance in patients with chronic heart failure. To determine the effect of milrinone on mortality, patients with severe chronic heart failure who remained symptomatic despite conventional therapy were randomized to receive either active drug or a matching placebo. The trial was terminated after 20 months, before its scheduled completion, based on an observed adverse effect of milrinone on survival. This paper describes the experience of the Data Monitoring and Safety Monitoring Board (DSMB) in dealing with an emerging negative trend in survival when there were other known beneficial effects of the drug.