Covidien completes enrolment in the DEFINITIVE AR study



Covidien has announced the completion of enrolment in its DEFINITIVE AR (Anti-Restenosis) study. As the third study in the DEFINITIVE trial series, this randomised pilot is designed to address the challenge of preventing restenosis, a common occurrence in patients with peripheral arterial disease (PAD).

According to the American Heart Association, approximately eight million people in the USA suffer from PAD.


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. Covidien announced initiation of this trial in August 2011. 


As shown in the DEFINITIVE LE study,1 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. According to a company release, 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.


The DEFINITIVE AR study is a multicentre, randomised study being conducted in Europe. Patients were randomised to one of two treatments: 1) directional atherectomy using the Covidien SilverHawk or TurboHawk plaque excision systems, followed by a drug-coated balloon using Cotavance Peripheral Paclitaxel-coated angioplasty catheter with Paccocath Technology (Bayer HealthCare), or 2) treatment with the Cotavance angioplasty catheter alone (without directional atherectomy prior to treatment). Enrolment in the randomised portion of the trial is complete. There is a third non-randomised 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 Gunnar Tepe, Klinikum Rosenheim in Germany, who is co-leading the DEFINITIVE AR study with Thomas Zeller, 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.2 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 revascularisation.


1. Lawrence Garcia M. DEFINITIVE LE 12 Month Final Results Paper presented at: VIVA 2012; Las Vegas, Nevada.

2. 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.