Enrollment Completed in Covidien's DEFINITIVE AR Study

January 15, 2013—Covidien (Mansfield, MA) announced the completion of enrollment in the DEFINITIVE AR (antirestenosis) study. As the third study in the company's DEFINITIVE trial series, this randomized pilot seeks to address the challenge of preventing restenosis in patients treated for peripheral artery disease (PAD).

According to Covidien's press release, 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 buildup, followed by the use of a drug-coated balloon that releases antiproliferative medication to inhibit restenosis.

The company noted that the DEFINITIVE LE study demonstrated that 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. Lawrence A. Garcia, MD, presented the DEFINITIVE LE study's final 12-month results in October during a Late-Breaking Trials session at the VIVA 2012: Vascular InterVentional Advances meeting in Las Vegas.

The DEFINITIVE AR study will investigate whether using a directional atherectomy device to remove plaque buildup beforehand increases the effectiveness of drug-coated balloons. This technique may improve the uniformity of drug delivery, thereby extending the amount of time the treated vessel stays open and reducing the need for subsequent treatments.

As summarized in the company's announcement, the DEFINITIVE AR study is a multicenter, randomized study being conducted in Europe. Patients were randomized to one of two treatments. One arm received directional atherectomy using the Covidien SilverHawk or TurboHawk plaque excision systems, followed by a drug-coated balloon using the Cotavance peripheral paclitaxel-coated angioplasty catheter with Paccocath technology (Medrad, Inc., Warrendale, PA, a part of the Medical Care division of Bayer HealthCare, Leverkusen, Germany). The second arm received treatment with the Cotavance angioplasty catheter alone, without directional atherectomy before treatment.

Covidien stated that enrollment in the randomized portion of the trial is complete. A third, nonrandomized arm in the trial 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 1 year.

The coleaders of the DEFINITIVE AR study are Prof. Gunnar Tepe, MD, of the Klinikum Rosenheim in Germany, and Prof. Thomas Zeller, MD, of the Universitäts-Herzzentrum Freiburg-Bad Krozingen in Germany.

“The ability of a drug-coated balloon to prevent restenosis may be diminished by the amount and type of plaque buildup in a patient's vessel,” commented Prof. Tepe in the Covidien press release. “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.”

Covidien's announcement noted that Prof. Tepe and Prof. Zeller were investigators in an earlier drug-coated balloon study called THUNDER, which was published in The New England Journal of Medicine in February 2008. 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.