To the surprise of absolutely no one, the latest forecast for the completion of the long-awaited IMPROVE-IT trial has been moved back a year to June 2013. Merck announced the change, which appeared on the IMPROVE-IT page on ClinicalTrials.Gov, in a press release (below) and a FAQ.

IMPROVE-IT, which is comparing Vytorin (ezetimibe/simvastatin) with simvastatin monotherapy in 18,000 patients, will continue until at least 5,250 subjects have a primary endpoint and are followed for at least 2.5 years. 16,000 patients have already been enrolled in the trial.

Merck also announced that, in addition to the previously scheduled interim analysis scheduled when 50% of the clinical endpoints have occurred, the Executive Committee of the trial and Merck have developed a plan for the Data and Safety Monitoring Board to conduct an additional interim efficacy analysis when 75% of endpoints have been reached.

A research report from Leerink Swann notes that because it is an efficacy analysis, the new interim analysis means that the trial ”will not be stopped for futility, only evidence of benefit or harm.” In addition, the new analysis slightly adds to the statistical burden of achieving a significant result in the trial.

Click here to read the research report from Leerink Swann

Click here to access the IMPROVE-IT page on ClinicalTrials.Gov

Click here to read previous coverage about Vytorin on CardioBrief.

Click here to read the Merck FAQ.

Here is the Merck press release:

Merck Statement on Clinicaltrials.gov Update Regarding the IMPROVE-IT Trial

WHITEHOUSE STATION, N.J., Jan. 7, 2010 – Merck submitted an update to clinicaltrials.gov to include a date of June 2013 as the new forecasted date for the completion of the IMPROVE-IT study. The revision is based on updated estimates reviewed by the IMPROVE-IT Executive Committee and Merck. The estimate for this event-driven trial reflects the most recent information on the pace of enrollment and the accumulation of clinical endpoints to date, and takes into account the minimum two and one-half years of follow-up called for in the study design.
It is difficult to predict specific conclusion dates for event-driven trials, particularly for large trials such as IMPROVE-IT, because of the variability in several factors, such as enrollment, discontinuation rates, and varying rates at which cardiovascular events occur. The Executive Committee and Merck will continue to monitor the progress of the study closely and update the timeline as appropriate.

There are currently approximately 16,000 patients enrolled in IMPROVE-IT; the study is planned to include up to 18,000 patients.

As previously disclosed, the Data Safety Monitoring Board will conduct an interim analysis for efficacy later this year when approximately fifty percent of the pre-specified (5,250) clinical endpoints have occurred. In addition, the IMPROVE-IT Executive Committee and Merck have developed a plan for the Data Safety Monitoring Board to conduct an additional interim efficacy analysis when approximately seventy-five percent of the pre-specified endpoints have been reached, which could result in an earlier completion of the study.

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