Screening, endpoint classification, and safety monitoring in the metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF)

The MERIT-HF study was designed to investigate the effect of once-daily dos ing of metoprolol succinate CR/XL added to standard therapy in patients wit h chronic heart failure. A screening programme, aiming at identifying eligi ble patients for the study was used by 231 out of 313 sites, resulting in 8 912 screened patients. These patients were older, more often women, had mar ginally higher ejection fraction and were more often in NYHA class IV compa red to the finally randomised patients. There was a positive correlation be tween the number of screened and randomised patients and due to the high in clusion rate the number of randomised patients was increased from 3200 to 3 991 patients. The clinical events were defined by a manual and were based o n identical classifications made independently by two members of an Indepen dent Endpoint Committee. Data from the case report form and the classificat ions made by the Endpoint Committee were in accordance for hospitalisation due to worsening heart failure on 722 occasions. On 207 occasions the data from the case report forms and the classification made by the committee dif fered regarding this clinical event. The Independent Safety Committee monit ored safety aspects of the study by using asymmetric group sequential proce dures. The study was stopped early on recommendation from the Independent S afety Committee, when the second pre-specified interim analysis (50% of tot al number of expected deaths) showed that the criterion for stopping due to benefit had been met and exceeded. In conclusion, a screening programme fa cilitated patient recruitment and showed the characteristics of the backgro und population, the event classification was improved by using an independe nt endpoint committee, and the safety monitoring allowed an early closure o f the study due to mortality benefit, without jeopardising the final analys es of the results. (C) 2000 European Society of Cardiology. All rights rese rved.