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 dosing of metoprolol succinate CR/XL added to standard therapy in patients with chronic heart failure. A screening programme, aiming at identifying eligible patients for the study was used by 231 out of 313 sites, resulting in 8912 screened patients. These patients were older, more often women, had marginally higher ejection fraction and were more often in NYHA class IV compared to the finally randomised patients. There was a positive correlation between the number of screened and randomised patients and due to the high inclusion rate the number of randomised patients was increased from 3200 to 3991 patients. The clinical events were defined by a manual and were based on identical classifications made independently by two members of an Independent Endpoint Committee. Data from the case report form and the classifications 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 differed regarding this clinical event. The Independent Safety Committee monitored safety aspects of the study by using asymmetric group sequential procedures. The study was stopped early on recommendation from the Independent Safety Committee, when the second pre-specified interim analysis (50% of total number of expected deaths) showed that the criterion for stopping due to benefit had been met and exceeded. In conclusion, a screening programme facilitated patient recruitment and showed the characteristics of the background population, the event classification was improved by using an independent endpoint committee, and the safety monitoring allowed an early closure of the study due to mortality benefit, without jeopardising the final analyses of the results.
Fagerberg
B
B
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden. bjorn.fagerberg@medfak.gu.se
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D018579:Patient Selection; D012449:Safety; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol