The abnormal heart rhythm known as atrial fibrillation (AF) carries a high risk of stroke, which is why many AF patients are put on a lifelong regimen of warfarin (Coumadin). But the side effects of this blood-thinning drug, mainly bleeding, can be dangerous. AGA Medical Holdings (Minneapolis) has introduced a new technology, the Amplatzer Cardiac Plug (ACP), that would fix the problem and eliminate the need for warfarin.
The percutaneous transcatheter device is intended to prevent thrombus embolization from the left atrial appendage (LAA) in patients who have nonvalvular atrial fibrillation. The ACP has just received a conditional investigational device exemption (IDE) approval from the FDA to evaluate the safety and efficacy of the device when used to close the left atrial appendage.
“The reason you potentially want the left atrial appendage closed is, if you're a patient with atrial fibrillation, the left atrial appendage remodels and gets thicker. There are lots of nooks and crannies – hiding places where clots have been shown to form. Those clots are associated with 90% of strokes. If you close it off and seal it, then you no longer have a place for clots to form and hide,“ Rachel Ellingson, senior director of AGA's business development, told Medical Device Daily.
The company is sponsoring a trial designed to demonstrate efficacy in preventing stroke in AF patients who are eligible to receive warfarin, as well as safety of the device and the procedure. The multicenter trial will include a two-to-one randomization between the ACP and medical management with warfarin, which is the current standard of care.
“Warfarin is a tough drug to tolerate,“ Ellingson said. “Many patients just can't tolerate it and it has a very narrow therapeutic window. If you take too much, you risk bleeding. If you take too little, there's not enough benefit.“
President/CEO John Barr said, “Stroke can be a debilitating condition, and is a significant concern to the approximately 4.5 million people in the U.S. and Europe suffering from atrial fibrillation. Approval of this study will now allow us to further evaluate our approach to reducing strokes in patients with atrial fibrillation by using our ACP to permanently seal the appendage, hopefully sparing patients from spending the rest of their lives on anticoagulants.“
Ellingson said the company has not yet disclosed study locations or the principal investigators. But she expects to have the first 400 patients enrolled sometime during the second half of 2010. An interim analysis will be performed after the first 400 patients are enrolled and at pre-determined periodic intervals thereafter, until a possible maximum of 2,000 patients are enrolled. These interval analyses will determine when the trial has achieved its endpoints and if AGA is able to conclude the trial prior to enrolling 2,000 patients.
The trial design will include a feasibility phase to be followed by a pivotal phase. The results of the feasibility phase, which consists of the first 30 patients to receive the ACP, will serve to further validate safety conclusions demonstrated through preclinical testing. These patients will be followed for 45 days after the procedure and evaluated for adverse events. The 45-day feasibility data will be reviewed by an independent data safety monitoring board prior to FDA review. Additional subjects will be enrolled in the pivotal phase of the trial after the FDA has completed its review.
The only other cardiac plug being developed in the U.S. is Atritech's (Plymouth, Minnesota) experimental Watchman. An FDA panel narrowly backed the device last spring, but the agency has since asked for a confirmatory trial to substantiate the effectiveness.
AGA is used to being a pioneer. In fact, last year, the company competed an initial public offering, raising $199.4 million, one of the few to succeed in the dismal market (MDD, Oct. 22 2009).
“We were the only medical device company to do an IPO last year,“ Ellingson said. “I think we truly view it as a significant testament to our company to go public when no other company could.“
The ACP received European CE mark approval in December 2008, and is currently sold in Europe, South America and parts of the Pacific Rim.
Lynn Yoffee; 770-361-4789;