Drug-Eluting Balloon Study Enrolls Participants: An Interview with Peter Schneider, MD

Medtronic, Inc. has completed enrollment in its IN.PACT SFA II trial, the US arm of its clinical study for the IN.PACT Admiral drug-eluting balloon (DEB) as a treatment for peripheral artery disease in the superficial femoral and proximal popliteal arteries (SFA and PPA). IN.PACT DEBs feature a proprietary coating called FreePac, formulated with paclitaxel and urea, an excipient that facilitates absorption of the drug into the vessel wall. 

The IN.PACT Admiral DEB received the CE mark in 2008 and 2009 and is available in many countries around the world.  In the United States, the IN.PACT Admiral drug-eluting balloon is limited to investigational use under an investigational device exemption granted by the US Food and Drug Administration (FDA). 

Results of the study will be combined with those from IN.PACT SFA I, which previously completed enrollment of 150 patients in Europe, to support a premarket approval (PMA) application to the FDA. Vascular Disease Management spoke with co-principal investigator Peter Schneider, MD, about the study and the device.

Q: Please give a brief overview of the study.

A: The incidence of peripheral arterial disease is increasing with an aging population and rise in diabetes, resulting in a dramatic rise in the number of limbs at risk for amputation.  This study was designed to evaluate the potential benefit of Medtronic’s IN.PACT Admiral, a drug-eluting balloon, compared to standard angioplasty treatment for the lower limbs. 

IN.PACT SFA II is a prospective, multicenter, randomized controlled trial that enrolled 181 patients at more than 40 US sites and randomized them 2:1 to treatment with either the IN.PACT Admiral drug-eluting balloon (study arm) or a traditional, non-coated angioplasty balloon (control arm).  

Patients enrolled in the study include those with symptoms of walking pain (claudication) and rest pain due to de novo or nonstented restenotic lesions in the superficial femoral and proximal popliteal arteries. The primary efficacy endpoint is primary patency, a measure of blood flow through the treated arterial segment, at 12 months. 

Complete details of the IN.PACT
SFA II study are available at the US National Institutes of Health clinical trials website at https://www.clinicaltrials.gov/ct2/show/NCT01566461?term=IN.PACT+SFA&rank=1.

Q: What is unique about this study?

A: Currently there are no DEBs approved in the US to treat the lower extremities. The IN.PACT program was designed as a 2-phase, randomized study to assess the safety and efficacy of the IN.PACT Admiral DEB.  IN.PACT SFA I was the first phase of the program and completed enrollment of 150 patients in Europe in April 2011. Results of IN.PACT SFA II will be combined with those from IN.PACT SFA I reporting on 331 patients to support a PMA application to the FDA.

 The ongoing global IN.PACT clinical program includes 29 studies involving more than 4,600 patients at approximately 230 sites worldwide.  Medtronic provides physicians outside the US with the necessary information to treat their patients with this new therapy.

 Q: What makes treatment with drug-eluting balloons promising?

A: IN.PACT DEBs provide localized drug delivery to fight restenosis and utilize a “leave nothing behind” strategy for treatment in the SFA  and  PPA.  Bare metal stents have improved patency, but there are significant dynamic stresses that make the SFA a challenge for a permanent implant. These challenges make an efficacious, stent-free option such as IN.PACT DEBs an attractive therapy for the peripheral space.  IN.PACT’s 9 presented and 6 published studies have shown promising safety and efficacy data.  Once the reduction in restenosis has been proven in a large scale pivotal study such as the IN.PACT SFA program, DEBs will prove to be economically beneficial for the healthcare system as the number of repeat procedures drops.  

Q: What are the limitations of DEBs?

A: Data on the benefit of DEBs in patients with highly calcified or extremely long lesions is early and needs to be investigated further. Medtronic recently began the IN.PACT Global study which will enroll 1,500 “real world” SFA patients globally.  This dataset will allow physicians to see the IN.PACT Admiral performance in more complex patient anatomies, including highly calcified or long lesions. 

Q: What is the current status of the study, and when will results be available? 

Medtronic announced completion of the US arm of IN.PACT SFA II in January 2013. This rapid enrollment reflects the enthusiasm of clinical investigators for this concept and potential tool.  Medtronic will be working with the FDA to finalize all inputs, clinical and other, needed for regulatory approval of the IN.PACT Admiral drug-eluting balloon in the US.

Q: Anything you’d like to add that is of particular importance for vascular specialists to know about this study and device?

A: Data on multiple DEBs is coming out, especially following the recent LINC 2013 meeting in Leipzig, Germany.  It is important for physicians to carefully review the data on DEBs coming on the market since there are differences in outcomes.  There is not a “class” effect and in other words, all DEBs do not perform with the same level of efficacy.  More patients have been treated with IN.PACT products than any other DEB, and the safety and efficacy performance has been well documented by the 9 studies presented and 6 published.

Peter Schneider, MD,  is a vascular surgeon and chief of the vascular therapy division at Kaiser Foundation Hospital and Hawaii Permanente Medical Group in Honolulu. Dr. Schneider reports consultancy to Impact Vascular, Royalties from Cook Medical, and reimbursements from Cordis and Medtronic, Inc.