Two PAD Trials Paused Over Paclitaxel Balloon, Stent Concerns

Patrice Wendling

December 19, 2018

Two trials in patients with peripheral artery disease (PAD) have suspended enrollment, citing newly published data suggesting a higher risk of death in patients with femoropopliteal lesions treated with paclitaxel-coated balloon and stents.

A meta-analysis, published online in the Journal of the American Heart Association December 6, showed a similar risk of all-cause death at 1 year among 4663 patients treated with paclitaxel-coated and noncoated devices in 28 randomized controlled trials.

The relative risk of all-cause death in the paclitaxel-treated device group, however, increased 68% at 2 years and 93% at 5 years. The absolute risk difference was 3.5% and 7.2%, respectively, and corresponding number-needed-to-harm was 29 patients at 2 years and 14 patients at 5 years.

Within days, organizers of the BASIL-3 and SWEDEPAD 1 and SWEDEPAD 2 trials announced they were suspending enrollment.

"Whilst the population of the reviewed trials differs from those in the BASIL-3 trial, it is clearly important new information that may cause concerns for the BASIL-3 trial in relation to patient safety," the BASIL-3 trialists said in a December 13 statement

"As such, it raises the need to consider whether changes to the trial protocol and patient information are required.  We have therefore decided to suspend recruitment to the trial, pending further discussions."

BASIL-3 is testing the clinical and cost-effectiveness of drug-coated balloons (DCB), drug-eluting stents (DES), and plain balloon angioplasty with bail-out, bare-metal stent revascularization strategies for severe limb ischemia secondary to femoropopliteal disease. The randomized controlled trial began its 3-year recruitment phase in 2016 and has enrolled 403 patients at 34 sites in England, Scotland, and Wales.

In an update the next day, the BASIL-3 trialists said its Trial Steering Committee had met and would likely complete a review of the meta-analysis by January. They would also be issuing a questionnaire to ascertain views pertaining to the use of drug-eluting technologies locally.

"We are currently considering whether this new information should alter our follow-up regime and whether we should inform patients," they said.

In a December 13 statement, the Swedish Drug-elution Trial in Peripheral Arterial Disease (SWEDEPAD) trialists announced that study management had met with its data safety monitoring committee (DSMC) as a result of the new meta-analysis.

"After DSMC performed an interim safety analysis of the study's pre-specified and monitored safety variables (occlusion rate, amputation rate and mortality by 30 days and one year) distributed on treatment allocation, the recommendation from DSMC is to promptly pause further inclusion in both SWEDEPAD 1 and SWEDEPAD 2," the trialists said.

"The study management is of the same opinion as DSMC and has today decided to stop inclusion in both sub-studies. On Monday [December 17], SWEDEPAD's steering committee meets and discusses the state of progress and further actions that need to be taken in response to this," they added.

No new announcement on the outcome of Monday's meeting had been posted as of press time.

SWEDEPAD consists of two parallel studies comparing revascularization with and without DCBs and/or DES in an estimated 3800 participants with PAD. Thus far, SWEDEPAD 1 has enrolled 1480 participants with critical limb ischemia and SWEDEPAD 2 has enrolled 810 patients with intermittent claudication.

Citing "recent concerns centered around drug-eluting devices and peripheral artery disease," VIVA Physicians announced plans to host an international forum on drug elution in PAD with recognized experts and representatives from major medical societies, the medical device sector, regulatory and reimbursement agencies, and patient advocates.

The event, titled "Drug Elution in Peripheral Artery Disease: A Critical Analysis From a Multispecialty Consortium," is planned for this February in Washington DC, according to an announcement last week from the nonprofit organization.

J Am Heart Assoc. 2018;7:e011245. Article

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