Clinical History

NMT Medical, Inc. has been at the forefront of supporting and sponsoring clinical trials in which transcatheter closure of various septal defects is compared to conventional therapy. In some cases, the trials were landmark trials marking the first time some patients received any treatment for their heart defects.

In 1996, NMT sponsored three major trials:

The CardioSEAL^® ASD trial – Europe enrolled over fifty patients at five leading pediatric cardiology centers in Europe. Patients had regular follow up for twelve months with excellent outcomes and very low complication rates. On the basis of this data, CardioSEAL^® was awarded the CE Mark.

The CardioSEAL^® ASD trial - USA, an FDA approved investigational trial comparing CardioSEAL^® closure of ASD to surgery. This trial intended to enroll over 200 patients in either the CardioSEAL^® or surgical arm, however shortly after initiation it became clear that patients would not participate in the trial, preferring not to take the chance of being randomized to surgery. Subsequent modifications of the trial eliminated that risk, but maintained a surgical cohort. In 1999, this trial was changed to add the STARFlex^® Occluder as the implant. Over 150 patients were enrolled, with very good results in small to moderate size atrial defects. Beginning in 2000, a continuation of this study was initiated and approximately another 150 patients were enrolled prior to closure of the study in 2002.

The Children’s Hospital Boston, High Risk Septal Defect Patient trial. In collaboration with the Cardiology division of Children’s Hospital Boston, NMT supported a clinical trial in which patients at high risk for surgical intervention to close their cardiac defect could be treated with CardioSEAL^®. This highly successful trial enrolled over 100 patients in just a few years, and was the basis of data used by NMT to gain three critical FDA approvals for patients with: Fenestrated Fontan defect; Ventricular Septal Defect; and PFO – recurrent Stroke. In 2000, this trial was updated to include the STARFlex^® Occluder. This trial remained active until 2003.

In 1998, NMT initiated a new trial, the PFO Stroke trial, in which CardioSEAL^® was evaluated against best medical therapy for prevention of recurrent stroke in patients with an unknown stroke source and PFO. As with the ASD trial, this trial was updated in 1999 to use the STARFlex^® Occluder, however, as with many randomized trials of the time, enrollment was difficult. In 2003, this trial was significantly modified and updated, putting control of the trial directly in the hands of stroke specialists. The new version of the trial called, The CLOSURE I clinical trial, was a first of its kind trial based on an extensive review of the vast observational science related to PFO – CVA closure being performed around the world. CLOSURE I was designed to enroll 1600 patients at over 100 centers in the United States and Canada, with patients being followed for two years. However in 2007, with enrollment slowed due to commercial availability of alternative devices, the enrollment target was reduced to 900 patients. In November 2008, NMT Medical announced enrollment in the CLOSURE I clinical trial was completed. At the present time, it is expected that data analysis will begin in the third quarter of 2010.

In 2002, NMT, working in close collaboration with two major US cardiology programs, began investigating an interesting finding by several physicians who had been using CardioSEAL^® to treat recurrent stroke PFO patients under the aforementioned FDA approvals. The finding was that in a subset of those stroke patients who also had migraine headaches, closure of the PFO led to cessation or reduction of the headaches. By late 2003, NMT had gathered compelling evidence of a strong clinical trend and in 2004 put together a Physician Advisory Group to assist the company in designing a “platform” clinical trial to formally investigate the trend with greater scientific rigor. Out of that effort, NMT initiated the first clinical trial evaluating PFO closure for Migraine relief – the MIST (Migraine Intervention with STARFlex^® Technology) trial, in late 2004.

MIST I was a 150 patient randomized, double blinded placebo controlled trial completed in the United Kingdom. Results from that trial indicated that refractory migraine patients with PFO would see statistically and clinically significant reduction in their headaches following PFO closure, even with a short follow up time frame of only six months The patients originally enrolled in this trial are continuing longer term follow up in a trial called MIST III.

Also in 2004 in the UK, a 50 patient Atrial Level Shunt trial – The BEST Trial - was initiated using NMT’s revolutionary BioSTAR^® implant. BioSTAR^® is the world's first bioabsorbable septal repair implant. The positive results of the BEST trial published in circulation resulted in the commercial approval of BioSTAR^® in the European community (CE Mark) and Canada (HPB) in late 2007.

Evaluation of the BioSTAR^® implant is ongoing in Europe and in Canada. Long term performance data is being evaluated through two active register studies: BRAVO (adult PFO patients) and BASIC (pediatric ASD patients).

NMT continues to lead the industry in developing clinical science related to PFO. We continually evaluate other medical conditions in which PFO may be a causative factor.

For more information, see our FDA Disclaimer

Technology

Clinical History

Quick Links