Medtronic has decided to recall and stop selling the IN.PACT Amphirion drug-eluting balloon after results from the IN.PACT DEEP clinical study indicated a trend towards a higher rate of major amputation in the drug-eluting balloon arm in patients with below-the-knee disease. The study also showed no benefit with the drug-eluting balloon compared to standard balloon angioplasty in terms of re-intervention and late lumen loss.
The IN.PACT DEEP study was a post-market, multicentre, randomised controlled trial to determine the safety and efficacy of treatment with the IN.PACT Amphirion drug-eluting balloon for below-the-knee revascularisation in patients with critical limb ischaemia. Pre-specified primary efficacy endpoints included clinically-driven target lesion revascularisation and late lumen loss. The primary safety endpoint was a composite of all-cause death, major amputation or target lesion revascularisation.
Three hundred fifty eight subjects were randomised 2:1 to either treatment with IN.PACT Amphirion or standard balloon angioplasty. After 12 months of follow-up, no difference was found between treatment and control groups in any of the three primary outcome measures. The study also identified a potential safety signal given a trend towards an increased rate of major amputations in the drug-eluting balloon study arm.
According to Medtronic, causality between major amputation and use of the IN.PACT Amphirion device could not be established or excluded. Subset and multivariate analyses of the data have not revealed any specific cause, and no other evidence from the trial has explained this finding. The IN.PACT DEEP 12-month results will be presented at a scientific session during the upcoming Leipzig Interventional Course (LINC) in Leipzig, Germany to be held 28–31 January 2014.
In a letter sent to the medical community on 11 November Medtronic stated, “Given the potential safety signal paired with no efficacy improvement seen in the study, Medtronic will voluntarily recall and stop sales of all IN.PACT Amphirion drug-eluting balloons.” The company added that it will continue to follow all patients in the IN.PACT DEEP study per protocol for up to five years and will continue to analyse data to better understand the longer-term patient outcomes.
Medtronic said that none of the company’s other drug-eluting balloons or peripheral products are affected. Specifically, the IN.PACT Admiral and Pacific drug-eluting balloons (for use in the superficial femoral artery) and the IN.PACT Falcon drug-eluting balloon (for use in coronary arteries) remain commercially available in markets where they are approved.
“We do not believe that the IN.PACT DEEP study outcomes carry any predictive value with regard to other drug-eluting balloon trials studying other anatomic districts. Multiple studies (six published) looking at drug-eluting balloons in the superficial femoral artery have shown positive and consistent outcomes with respect to patency, target lesion revascularisation and adverse events.
In the letter, Medtronic also noted that “the large differences between below-the-knee and superficial femoral artery disease (greater peripheral arterial disease severity, presence of wounds and smaller vessel diameters) may be a potential cause of the very different outcomes seen.”
Medtronic said it remains committed to the below-the-knee space. “Patient needs are high and there is an opportunity to improve current clinical outcomes. We plan to launch a new microcatheter, specifically designed for crossing difficult below-the-knee lesions, in the next year and will continue to develop other products to advance the treatment of below-the-knee disease. We will continue to investigate the outcomes of the IN.PACT DEEP study in order to better understand the cause of the signals seen and then determine how best to move forward with below-the-knee drug-eluting stent therapy.”
Looking ahead, Medtronic reiterated its plan to present the results from the IN.PACT SFA I and II clinical studies for the first time at the Charing Cross Symposium in London (5–8 April 2014). Data from these two randomised controlled trials will support the company’s pre-market approval application to the US Food and Drug Administration for the IN.PACT Admiral drug-eluting balloon.