W.L. Gore & Associates (Flagstaff, Arizona) has received the green light from FDA to conduct the Gore REDUCE clinical study for its Gore Helex Septal Occluder to be used in patent foramen ovale (PFO) closure to prevent recurrent stroke.

Gore is the third company to receive approval for such a study from the FDA.

"There are other companies that are going down this path," Mike Markert, marketing coordinator for the Gore Helex in Gore's Medical Products Division, told Medical Device Daily in reference to the companies seeking ways to treat PFO. It's not so much of an uncharted territory."

PFOs occur naturally during pre-natal life, but they may persist into adulthood in as many as three in 10 cases. This hole between the left and right atria can allow unfiltered blood back into circulation, raising the risk for strokes.

AGA's (Plymouth, Minnesota) current PFO closure device, the Amplatazer, is in a Phase III trial that commenced last October, and in that study, the firm proposes a link between PFOs and migraine headaches.

NMT Medical (Boston) is enrolling patients in a trial for its Starflex closure device under the hypothesis that PFO closure can prevent stroke.

In March of last year, an advisory panel of the FDA heard pleas from NMT about allowing the company to market its products without undergoing randomized, controlled clinical trials (RCTs) (Medical Device Daily, March 6, 2007). The attempt was unsuccessful, with RCTs remaining the "gold standard" for FDA to evaluate the effectiveness of PFO closure.

The circulatory systems advisory panel addressed this question previously in 1997, when the panel concluded that RCTs were necessary for this application and that assessment should include freedom from recurrent stroke.

Gore's study would evaluate the effectiveness of its Gore Helex Septal Occluder in PFO closure. The Gore Helex Septal Occluder is said by the company to be the first device of its kind to use ePTFE, a biocompatible material that allows progressive tissue in-growth, to help seal the defect.

The device has been designed to be soft and flexible, conforming to the anatomy of the heart while bridging and covering the defect to stop the shunting of blood between the atria a key difference, the company says from other PFO devices.

"The device is a catheter-based device that unfolds on the side of the defect," Markert told MDD. "When it's deployed, the way it wraps around the defect is reminiscent of a DNA helix hence its name."

He said the company already has FDA approval for the device, but under a different designation. "Specifically the device is approved to treat atrial septal defects (ASD), congenital heart defects that often involve young children. We received FDA approval for that indication in September 2007."

In Europe, the practice of PFO closure is widely accepted, and there is no need for a trial or study to garner CE-mark status for the procedure. The device has been widely utilized for the closure of both ASD and PFO in Europe since 1999.

Patients in the Gore study will be randomized and split into one of two treatment arms, either antiplatelet medical management alone or device closure of the PFO in conjunction with antiplatelet medical management. The primary goal is freedom from recurrent ischemic stroke, imaging-confirmed transient ischemic attack, or death due to stroke through 24 months post-randomization.

In all, there are expected to be 600 patients featured in the study in 50 sites stretching outside U.S. borders.

One of the biggest problems for the FDA is off-label use of devices to treat PFO closure. The conundrum has led to a bigger push for the agency to have companies engaged in RCTs to prove device effectiveness.

The problem is that the typical patient does not want an invasive procedure unless the doctor can guarantee the outcome and only if there is no alternative, but most patients also prefer to avoid a lifetime drug regime. Attitudes toward medications change throughout time and patients see closing the hole as a desirable alternative if the procedure isn't too bad. Also, the fact that the PFO closure procedure can be done as an outpatient procedure lowers the resistance.

But Gore said it expects validation that such validation would cut into this off-label use.

"If the study is successful, then we would be able to demonstrate to the FDA its effectiveness and expand the designation of the device," Markert said.

He didn't have a timetable of when the company expected the approval to come, but hinted that immediately following any such approval the product would be made readily available for PFO closure.

Gore is a privately held company begun in 1958, when Bill and Vieve Gore set out to explore opportunities for fluorocarbon polymers, especially polytetrafluoroethylene. Within the first 12 years, Gore had wire and cables on the moon and operations worldwide.

The company now has nearly 8,000 associates in more than 45 locations around the world and annual revenues that top $2 billion.