Medical Device Daily Associate Managing Editor

NMT Medical (Boston) reported that it has received conditional approval from the FDA for modifications the company requested to its current investigational device exemption (IDE) for its pivotal patent foramen ovale (PFO) migraine clinical study, MIST II (Migraine Intervention with StarFlex Technology).

The company said the changes are supported by its previous trials – MIST and BEST (BioStar Evaluation STudy).

The FDA granted approval to adjust the primary endpoint for the study from resolution to reduction of migraine headaches and to upgrade the implant used in the study from the Starflex to NMT's new bioabsorbable implant, BioStar.

MIST II's modified design will evaluate the safety and effectiveness of NMT's catheter-based implant technology for the treatment of migraine headaches in patients with a PFO.

The clinical study seeks to enroll about 600 migraine patients, who will either receive an implanted device or a fake procedure to test for the placebo effect.

It appears that the company decided to alter the trial based on its experience with the first MIST trial with the StarFlex. In March results reported on at the American College of Cardiology (ACC; Bethesda, Maryland) showed that the MIST trial failed to meet its goal of eliminating at least 40% of migraine headaches after six months (Medical Device Daily, March 14, 2006).

Also, the company apparently made good on a promise to retool the MIST II trial after the endpoint miss with its predecessor.

In a conference call after the MIST presentation in March, John Ahern, NMT president/CEO said the company was in the process of identifying elements of that trial that it could take to the FDA to help make any relevant changes to the MIST II, “so that it's a more robust study with a higher chance of success.”

A PFO is a common heart defect that may be a potential risk factor for migraine headaches in some patients. The PFO allows venous blood, unfiltered and unmanaged by the lungs, to enter the arterial blood circulation. The unfiltered venous blood may contain elements that can trigger migraines in some patients.

The prevalence of migraines in the U.S. is about 10%. Of the 28 million migraine sufferers in the U.S., those who experience aura and have a PFO may represent a three million patient subset, according to NMT.

“The approved clinical trial changes represent an important milestone for NMT and will benefit patients and our clinical partners in several ways,” said Ahern in a statement. “First, we believe patients participating in the MIST II study will benefit from the advantages of our latest PFO closure technology, BioStar, including faster healing and more complete closure. Second, the MIST II clinical research team and the patients they enroll will participate in the only PFO/migraine clinical trial designed to reflect clinical evidence from a predicate PFO/migraine study, MIST. Lastly, we believe that the MIST II changes extend the company's leadership position in PFO clinical research and technology.”

As a result of the changes, Ahern said the company has “transformed MIST II into a stronger, U.S.-based PFO/migraine study with a clinically relevant primary endpoint.”

NMT's recently completed BEST study reported that the BioStar achieved a post-implant complete closure rate of 92% at 30 days and 96% at six months. Over time, 90% to 95% of the BioStar implant is absorbed and replaced with the patient's native tissue providing a more natural closure of the PFO.