January 16, 2013 — Covidien announced the completion of enrollment in its DEFINITIVE AR (anti-restenosis) clinical study. As the third study in the DEFINITIVE trial series, this randomized pilot is designed to address the challenge of preventing restenosis (re-narrowing of a blood vessel following treatment), a common occurrence in patients with peripheral artery disease (PAD).
According to the American Heart Association, about 8 million people in the United States suffer from PAD. PAD affects blood vessels throughout the body. When the vessels become clogged with plaque, blood flow slows or stops. If left untreated in the legs or feet, for example, this condition can lead to severe pain when walking, gangrene and even amputation.
The DEFINITIVE AR study is designed to evaluate the effect of treating a diseased vessel with a combination therapy that begins with directional atherectomy to remove plaque build-up, followed by the use of a drug-coated balloon that releases anti-proliferative medication to inhibit restenosis. As shown in the DEFINITIVE LE study,  directional atherectomy is effective in treating PAD without leaving a permanent implant behind. While the use of drug-coated balloons to treat PAD has demonstrated reduced vessel narrowing, there has been limited clinical study of the effectiveness of this treatment in calcified lesions. Using a directional atherectomy device to remove plaque build-up beforehand may increase how well drug-coated balloons work by improving the uniformity of drug delivery and thereby extending the amount of time the treated vessel stays open and reducing the need for subsequent treatments.
“Covidien is committed to building upon the growing body of clinical evidence for the use of directional atherectomy in the treatment of complex PAD,” said Mark A. Turco, M.D., chief medical officer, Vascular Therapies, Covidien. “We are eager to see the results of DEFINITIVE AR and to understand if this combination therapy of debulking followed by anti-restenotic therapy could lead to improved drug delivery and improved patient outcomes.”
DEFINITIVE AR Study Design
The DEFINITIVE AR study is a multi-center, randomized study being conducted in Europe. Patients were randomized to one of two treatments: 1) directional atherectomy using the Covidien SilverHawk or TurboHawk plaque excision systems, followed by a drug-coated balloon using Bayer HealthCare’s Cotavance Peripheral Paclitaxel-coated angioplasty catheter with Paccocath Technology, or 2) treatment with the Cotavance angioplasty catheter alone (without directional atherectomy prior to treatment). Enrollment in the randomized portion of the trial is complete. There is a third non-randomized arm in the trial that is still enrolling patients with heavily calcified PAD. All patients in this arm are being treated with directional atherectomy followed by the Cotavance angioplasty catheter. Patients in the study will be followed for one year.
“The ability of a drug-coated balloon to prevent restenosis may be diminished by the amount and type of plaque build-up in a patient’s vessel,” said Prof. Gunnar Tepe, M.D., Klinikum Rosenheim in Germany, who is co-leading the DEFINITIVE AR study with Prof. Thomas Zeller, M.D., of the Universitäts-Herzzentrum Freiburg - Bad Krozingen, also in Germany. “Removing plaque with directional atherectomy prior to treatment with a drug-coated balloon may enhance durability of outcomes through increased drug penetration and uptake into smooth muscle cells.”
Tepe and Zeller were investigators in an earlier drug-coated balloon study called THUNDER. This trial, along with other subsequent studies, found that the use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization.
For more information: www.covidien.com
1. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA:The Journal of the American Medical Association. Sep 19 2001;286(11):1317-1324.
2. Lawrence Garcia M. DEFINITIVE LE 12 Month Final Results Paper presented at: VIVA 2012; Las Vegas, Nevada.
3. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. Feb 14 2008;358(7):689-699.
Paccocath and Cotavance are trademarks of Bayer Pharma AG.