Clinical trial design, endpoints and regulatory considerations in heart failure

Following the withdrawal of flosequinan in the early 1990s due to heightened mortality and fatal arrhythmia risks, regulatory agencies have demanded evidence of the efficacy of novel treatments in managing heart failure, with mortality and morbidity endpoints becoming more stringent criteria for approval. In recent times, regulatory agencies have exhibited a greater willingness to permit the evaluation of functional capacity as an efficacy endpoint, albeit limited to specific patient groupings. Consequently, a novel therapeutic intervention for heart failure may be granted approval provided that it enhances survival rates, decreases length of hospital stays, and/or safely improves functional capacity. This article reviews clinical trial design, trial endpoints and regulatory issues in heart failure trials.