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.
KeywordsChronic Heart Failure NYHA Class Severe Chronic Heart Failure Positive Inotropic Agent Promise Trial
Unable to display preview. Download preview PDF.
- 4.Jain P, Brown EJ Jr, Langenback EG, et al. 1991. Effects of milrinone on left ventricular remodeling after acute myocardial infarction. Circulation 84:796–804.Google Scholar
- 6.Packer M, Leier CV. 1987. Survival in congestive heart failure during treatment with drugs with positive inotropic actions. Circulation 75:Suppl IV:IV-55–IV-63.Google Scholar
- 10.Chesebro JH, Browne KF, Fenster PE, Garland WT, Konstam MA. 1988. The hemodynamic effects of chronic oral milrinone therapy: a multicenter controlled trial. J Am Coll Cardiol 11:144A. abstractGoogle Scholar
- 17.US Food and Drug Administration (2001) Draft Guidance for Clinical Trial sponsors on the establishment and operation of Clinical Trial Data Monitoring Committees. Rockville, MD: FDA. http://www.fda.gov/cber/gdlns/clindatmon.htmGoogle Scholar
- 20.Friedman LM, Furberg CD, DeMets DL. 1998. Fundamentals of Clinical Trials. Third Edition, Springer-Verlag, New York.Google Scholar