The forecast completion date for a large-scale clinical trial comparing cardiovascular outcomes with Merck & Co’s Vytorin (simvastatin + ezetimibe) and with simvastatin (Zocor) alone has been set back to June 2013 in the face of slow patient enrolment.

The IMPROVE-IT study was previously expected to be over in 2012. Merck & Co posted an update on the online registry clinicaltrials.gov stating that the revised completion date “reflects the most recent information on the pace of enrolment 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”.

So far some 16,000 patients have enrolled in IMPROVE-IT, a randomised, active-control, double-blind Phase III trial evaluating the clinical benefit of Vytorin, Merck & Co’s controversial cholesterol-lowering drug, versus simvastatin 40mg in subjects with stabilised high-risk acute coronary syndrome. The enrolment target is up to 18,000 patients.

“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 enrolment, discontinuation rates, and varying rates at which cardiovascular events occur,” Merck & Co commented. “The [IMPROVE-IT] Executive Committee and Merck will continue to monitor the progress of the study closely and update the timeline as appropriate.”

The company also confirmed that the Data Safety Monitoring Board for the IMPROVE-IT trial would conduct an interim analysis for efficacy later this year, when around 50% of the pre-specified 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 a further interim efficacy analysis when around 75% of the pre-specified endpoints have been reached. This “could result in an earlier completion of the study”, Merck & Co noted.

The primary outcome measure for IMPROVE-IT is the effect of Vytorin versus simvastatin monotherapy on death due to any cardiovascular events, non-fatal coronary events (e.g., heart attack) and non-fatal strokes.

The significance of the IMPROVE-IT trial has been magnified by the welter of negative publicity around the ENHANCE study, which raised questions over whether Vytorin worked any better than the far cheaper simvastatin on its own.

The ENHANCE controversy has hit sales of Vytorin, although there was better news for Merck & Co last month when the US Food and Drug Administration (FDA) said the product was unlikely to be associated with an increased risk of cancer. That was tempered, though, by the first stirrings of generic competition, as Mylan filed an Abbreviated New Drug Application with the FDA for its version of the simvastatin/ezetimibe combination.