Patients with critical limb ischemia experienced two-and-a-half-fold higher amputation rates when physicians used paclitaxel-eluting IN.PACT Amphirion drug-eluting balloons (IA-DEB) as opposed to percutaneous transluminal angiography (PTA). Although the trial met its noninferiority threshold, findings resulted in the manufacturer pulling the device from the market.
These results were published online Oct. 15 in the Journal of the American College of Cardiology.
Lead author, Thomas Zeller, MD, of the Universitäts Herzzentrum Freiburg Bad Krozingen in Germany, and colleagues wrote, “It is worth noting that the IN.PACT DEEP trial results only apply to the specific IA-DEB study device for BTK [below the knee] revascularization. Positive results on the use of IN.PACT and other DEB technologies have been consistently reported for the femoropopliteal vascular territory, which may likely derive from known differences in the severity of vascular disease and DEB technologies”
IN.PACT-DEEP (The Study of IN.PACT Amphirion Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia) trial compared 358 patients divided two-to-one between IA-DEB (Medtronic) and PTA for treatment. The multicenter, prospective, randomized and controlled trial assessed clinically driven target vessel revascularization and late lumen loss as primary efficacy endpoints through 12 months. Major amputation, all-cause mortality and clinically driven target vessel revascularization were also assessed as a composite at six months as part of assessing safety.
At baseline, 84.1 percent of IA-DEB and 77. 3 percent of PTA patients presented with Rutherford Category five; 14.2 percent and 17.6 percent, respectively, presented with Rutherford Category four; and 1.7 percent and 4.2 percent, respectively, were Rutherford Category six.IA-DEB was used on shorter lesions with more restricted flow than PTA. The 12-month revascularization rate in the amputation-free patients was 9.2 percent and 13.1 percent for IA-DEB and PTA, respectively. In the whole population of patients, IA-DEB and PTA had target lesion revascularization rates of 11.9 percent and 13.5 percent, respectively, with no difference between binary restenosis or occlusion rates between the two at 12 months.
Composite major amputation, all-cause mortality, and clinically driven target vessel revascularization were experienced in 17.7 percent of IA-DEB patients and 15.8 percent of PTA patients. Amputation as a separate endpoint was observed as being 8.8 percent among IA-DEB patients and 3.6 percent among PTA patients through 12 months.
While other femoropopliteal studies showed other IN.PACT DEB to be both safe and effective, the less positive outcomes seen with this version of the device, targeting infrapopliteal artery revascularization, led to speculation.
Comments made by John R. Laird, MD, of the University of California, Davis Medical Center in Sacramento, and Ehrin J. Armstrong, MD, of the Colorado School of Medicine in Aurora, suggested that the balloon’s construction and coating were likely to blame. The balloon, they noted, was made of different material and coated in the drug in a closed position, leaving the bulk of the drug subject to loss before it reached the lesion. “The lack of an observed treatment effect in the current study might well be explained by an insufficient paclitaxel dose delivered into the vessel wall,” Laird and Armstrong wrote.
This study was funded by Medtronic, Inc.