April 10, 2009 - NMT Medical Inc. said this week data analysis for its STARFlex device for patent foramen ovale (PFO)/stroke and transient ischemic attack (TIA) clinical trial, CLOSURE I, will remain scheduled for the fourth quarter of 2010.
The company then expects to submit a pre-market approval (PMA) application for its STARFlex device for the stroke and TIA indication to the U.S. Food and Drug Administration (FDA) soon after the data analysis is completed.
With the approval of the trial’s Executive Committee, NMT recently received the findings of an independent statistical review committee regarding the timing of CLOSURE I data analysis. The independent statistical committee comprised of biostatisticians and trial design experts, whose charter had been previously approved by the FDA, determined that it was “highly likely” that sufficient primary outcome events (strokes and TIAs) would have occurred so that an analysis could be performed in October 2009 - one year earlier than originally planned. At that time, 93 percent of the trial data will be available and all patients will have completed at least one year of follow-up. However, while an early event driven analysis may be statistically valid, the CLOSURE I Executive Committee advised that the conservative pathway that offers the best statistical power to observe a significant difference in treatment alternatives would be to follow the original trial timeline. As a result, NMT has decided at this time to maintain the two-year timetable for data analysis.
NMT said the trial might provide the clinical stroke community with an early answer to one of the most important and vexing problems in stroke neurology today - whether PFO closure prevents ongoing damage to the brain from recurrent strokes and TIAs.
The trial is being led by Principal Investigators Anthony Furlan, M.D., and Mark Reisman, M.D. Dr. Furlan is chairman, department of neurology, Neurological Institute University Hospitals Case Medical Center, and Case Western Reserve University School of Medicine in Cleveland. Dr. Reisman is director, cardiovascular research and director, cardiac catheterization lab, Swedish Heart and Vascular Institute in Seattle.
“The results from CLOSURE I will provide valuable insight on how to best reduce recurrent stroke risk in patients with a PFO,” Dr. Furlan said. “The trial is designed to determine if PFO closure is a more effective treatment than medical therapy alone for patients with cryptogenic stroke and TIA. While the medical community eagerly awaits the results of this important trial, we applaud NMT’s current decision to maintain the original data analysis timetable, which will provide maximum statistical power. On the other hand, it is of some reassurance that the independent statistical committee indicated that we will likely have enough primary outcome events to detect a significant result as early as October 2009.”
“This landmark study and its anticipated results have generated a high level of interest within both the cardiology and neurology communities,” said Dr. Reisman. “However, there is no scientific advantage to changing the decision about the timing of the data analysis today.”
Martin concluded, “We all are eager to uncover the connection between PFO, stroke and TIA, but we decided not to accelerate the data analysis schedule at this time. We would like to acknowledge and thank the more than 190 leading stroke neurologist and interventional cardiologist investigators, their research teams, the enrolled patients, and our employees and shareholders for their continued commitment to the CLOSURE I trial.”
A PFO is a common heart defect that may be a potential risk factor for stroke, TIA, migraine or other brain attacks in some patients. The PFO allows venous blood, unfiltered and unmanaged by the lungs, to enter the arterial blood circulation. CLOSURE I is designed to evaluate the effectiveness of NMT’s STARFlex implant technology in preventing recurrent stroke and/or TIA due to a presumed, paradoxical embolism through a PFO. More than 190 leading stroke neurologists and interventional cardiologists at approximately 95 centers in the U.S., Canada and the U.K. are participating in the study. Of the 910 stroke and TIA patients enrolled, half received PFO closure in a catheter-based procedure with NMT's STARFlex implant and half were treated with drugs alone.
For more information: www.nmtmedical.com