January 24, 2008 (Boston, MA) - NMT Medical announced today that it is halting MIST II, its US-based trial evaluating the use of its patent foramen ovale (PFO)–closure device to treat migraine with aura. According to the statement released by NMT today, the company's decision to halt MIST II is due in part to difficulties enrolling patients in the trial and in part to the need to channel funding toward NMT's investigation of PFO closure for stroke, in particular the company's pivotal CLOSURE I trial. MIST II had been under way at 20 US centers, but out of more than 1400 migraine patients screened for enrollment, "only a handful" actually met requirements for randomization, the statement reads.
"While NMT continues to believe in the relationship between PFO and migraine, it has become clear that an acceptable enrollment dynamic was not possible, and completing the study would require more time and financial resources than we are willing to commit at this time," NMT president and CEO John E Ahern is quoted in the press release.
MIST trial program in the spotlight
NMT's MIST trial program has been under increased scrutiny since October 2007, when the co-principal investigator for the trial, Dr Peter Wilmshurst (Royal Shrewsbury Hospital, UK), told attendees of a TCT 2007 session that he had concerns about how the MIST I data were managed and reported. Wilmshurst and co-PI Dr Andrew Dowson (Kings College Hospital, London, UK) first presented the MIST I results publicly at the ACC 2006 Scientific Sessions, showing no benefit to PFO closure for the primary end point of the trial--headache cure--but promising secondary findings in terms of reductions in headache days. But as reported by heartwire , Wilmshurst now alleges that the study sponsor has misrepresented the data, denied the existence of a review that questioned device success in the trial, and repeatedly blocked access to the full data set. NMT spokespeople, in response, have rejected Wilmshurst's claims, saying he was never in fact a co-principal investigator for the study and was dropped as a trial investigator for "protocol violations."
As reported by heartwire , other experts have subsequently called for an independent review of the MIST I data, although the company insists that such a review cannot be performed without patient consent. It has been almost two years since the MIST I results were presented, yet the results have still not been published; NMT's press release today asserts that the study is "expected" to be published in Circulation early this year.
In its announcement today, NMT says it hopes to save approximately $14 million over the next few years by redistributing funding that had originally been budgeted for MIST II. Also quoted in the press release, co-principal investigators for MIST II, Dr Stewart Tepper (Yale University, New Haven, CT) and Dr Mark Reisman (Swedish Medical Center, Seattle, WA), used words like "difficult," "necessary," and "appropriate" to describe NMT's decision. Reisman, a cardiologist, also emphasized that he is still committed to evaluating the connection between migraine and PFO.
Commenting on the company's announcement for heartwire , Dr Roxana Mehran (Columbia University, New York, NY) said that she believes "absolutely" that PFO closure for migraine is worth further investigation but appreciates that the company was in a tough position.
"Frankly I'm not surprised by the decision. They have acted with some sound judgment. Given the strict entry criteria for the trial, they had to screen many, many patients, and if you have to screen that many people to yield just a handful of eligible patients, you risk ending up with trial results that may not be applicable to the wide range of migraine patients."
She says the onus is back on scientists and researchers to come up with the right trial design to investigate the link between PFO and migraine, noting that at least two other companies have trials investigating PFO closure for migraine. "I think the connection between PFO and migraine is one that is very interesting and merits further study. If you have a safe and effective device and a safe procedure, you may be able to give quality of life back to millions of migraine sufferers: I do believe there is a huge future here."
She rejected the suggestion that any problems with MIST I may be behind the company's decision, saying that MIST I served the role of being hypothesis-generating but perhaps was "too aggressive" in its end points.
NMT's CLOSURE I trial, along with other pivotal trials by different sponsors investigating PFO closure for stroke/transient ischemic attack, has also struggled with sluggish patient enrollment. Today's announcement by NMT, however, notes that CLOSURE I is now close to finishing enrollment.
Mehran disclosed that the Cardiovascular Research Foundation, where she is director of clinical research, receives research support from Coherex, a company developing a PFO-closure device. She also receives research support from Tyco/Mallinkradt, Guerbet, Cordis/J&J, and Boston Scientific and is on the speaker’s bureau for The Medicines Company.
Heartwire from Medscape © 2008 Medscape
Cite this: Shelley Wood. NMT Announces Termination of Its MIST II Trial of PFO Closure for Migraine - Medscape - Jan 24, 2008.