FDA panel favors approval of new AAA stent graft system

The FDA Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 11-4 that the benefits of a device designed for the endovascular treatment of infrarenal abdominal aortic aneurysm outweigh the potential risks.

Although the panel also voted 14-0 with one abstention that the Incraft AAA Stent Graft System (Cordis) is reasonably effective in the population for which the device would be indicated, it remained split 11-4 on the question of safety.

The decisions followed considerable discussion of data from the multicenter, prospective, nonrandomized INSPIRATION trial. Although the study met its primary efficacy and safety endpoints, results from follow-up out to 5 years raised concerns, showing higher-than-anticipated rates of certain events, including transrenal stent fractures, device occlusions and patency-related events, aneurysm expansion and endoleaks.

Ultimately, the stent graft’s ultra-low-profile design and potential benefit for patients with smaller access vessels or tortuous anatomy appeared to play a role in the committee’s vote. Richard Page, MD, from the University of Wisconsin School of Medicine and Public Health, who, as committee chair, did not get a vote, noted that he did not believe the benefits of the device outweighed the risks, but supported the decision.

“It appears that the device meets an unmet need,” he said during his concluding remarks to the panel. “My sense is that none of you would use it for an uncomplicated patient, but our vascular surgery colleagues want it available to them, so they should have that tool.”

Unanswered questions

Despite meeting its primary safety and efficacy endpoints, the INSPIRATION trial, which enrolled 190 patients (mean age, 73.9 years; 90% men) showed that 10% of patients had at least one transrenal stent fracture — a rate that is higher when compared with other investigational device exemption studies (IDE) for similar devices, the FDA noted.

The majority of stent fractures were identified by the core lab, as opposed to the site lab, and it was noted that the sponsor switched to a second core lab during the study.

Although committee members agreed that fewer stent fractures would be preferable, some noted that increased identification of stent fractures may be attributable to improved imaging. They were also encouraged by the lack of fractures in the main body of the graft or stent graft material and the fact that there has been very little migration.

“The idea of a stent fracture sounds really scary, but I think it happens all the time, I think it happens more with nitinol stents, I think it happens more in the superficial femoral artery and we aren’t using high-quality imaging techniques,” Brandon W. Propper, MD,

FACS, RPVI, from the San Antonio Military Medical Center, said during the panel discussion. “While I understand the concern presented in the data and ideally would love to have no stent fractures, the reality is that we don’t have devices for everything we need to treat, so we have to use the best available technology to fix complicated problems.”

Nevertheless, committee members agreed that more follow-up is necessary.

“I have concern that we don’t have enough data at 4 to 5 years,” Amy B. Reed, MD, from the University of Minnesota, said. “Will those stent fractures that are currently not an issue be an issue down the road?”

The frequency of type 1 endoleaks also appeared to be higher when compared with other IDE studies, as was the rate of type 2 endoleaks. Importantly, the FDA noted, the rate of aneurysm expansions in INSPIRATION, most of which was attributable to type 2 endoleaks, was higher than the rates in other IDE studies.

Panel members remained concerned about the greater frequency of endoleaks and aneurysm expansion, but many noted that a number of factors, including patient selection as well as the difficulty inherent to comparing trials, may be to blame.

In terms of other concerns, including occlusions and other patency-related events, the committee was divided. Some panel members attributed the higher event rates to the inclusion of patients with more complex anatomy in this trial, but said the findings were balanced by the significant benefit also seen in this higher-risk patient population. Others, however, maintained that they could not draw the same conclusion from the available data and the device would still not be their first choice, even in patients with more complex anatomy.

Looking ahead

Despite the panel’s favorable decision, all members emphasized the need for more data and a clear description of the risks associated with the device and the signals observed in the INSPIRATION trial.

The sponsor proposed a multicenter, prospective, open-label, observational post-approval study that will include 150 patients from the INSIGHT study — the post-approval study in Europe — and 150 de novo patients at study sites in the United States. Follow-up will occur at 30 days, 1 year and annually through 5 years, with treatment any other medical therapy to be provided according to standard clinical practice.

During their discussion, panel members noted that the post-approval study requires “significant work” in terms of the endpoints, number of patients, inclusion of more women and protocol regarding core-lab ascertained events.

The Incraft device is a modular bifurcated endovascular graft system that is composed of an aortic bifurcate prosthesis and an iliac limb prosthesis, both of which are preloaded into the delivery system and advanced to the intended location under fluoroscopy where it is deployed to exclude the aneurysm sac from blood flow.

The proposed indication for use of the stent graft system includes endovascular treatment of infrarenal AAA in patients with adequate iliac or femoral vessel morphology that is compatible with vascular access techniques, devices and accessories; proximal neck length of 10 mm or greater; aortic neck diameters between 17 mm and 31 mm; aortic neck suitable for suprarenal fixation; infrarenal and suprarenal neck angulation of 60 degrees or less; iliac fixation length of 15 mm or greater; iliac diameters between 7 mm and 22 mm; and minimum overall AAA treatment length of 128 mm or greater.

“We are pleased with the panel’s recommendation today, which brings us one step closer to making the Incraft system available for thousands of high-risk patients in the U.S.,” Shaden Marzouk, MD, chief medical officer at Cardinal Health, the parent company of Cordis, said in a press release. “We appreciated the opportunity to present our data supporting the Incraft system and look forward to continuing discussions with the FDA to bring this technology to doctors and patients.”

The FDA is not required to follow the recommendations of its advisory committees, but it usually does. – by Melissa Foster

Disclosure: One panel member reports his institution received research grants for participation in the INSPIRATION trial.