January 29, 2014
IN.PACT DEEP Drug-Eluting Balloon Data Show No Differential Treatment Effect, Trend Toward Increased Amputation Rate in Below-the-Knee CLI Patients
January 29, 2014—New data from the IN.PACT DEEP clinical trial were presented by Prof. Thomas Zeller during LINC 2014: The Leipzig Interventional Course in Leipzig, Germany. In the study, use of the In.Pact Amphirion drug-eluting balloon [(DEB) Medtronic, Inc. (Santa Rosa, CA)] did not result in a differential treatment effect for patients with below-the-knee critical limb ischemia (CLI) as compared to use of a standard percutaneous transluminal angioplasty (PTA) balloon.
The study also showed a safety signal in the DEB arm—specifically, a trend toward an increased rate of major amputation (above the ankle) compared to the PTA control. Causality between major amputation and use of the In.Pact Amphirion DEB could neither be established nor excluded.
Based on these findings, Medtronic voluntarily withdrew the IN.PACT Amphirion DEB from all markets worldwide in November 2013. The company issued a statement on December 4 announcing the recall. No other Medtronic DEB products were involved in IN.PACT DEEP or subject to the recall of the In.Pact Amphirion DEB; these other products remain on the market in countries where they have been approved. Medtronic noted that multiple studies—14 presented and six published—support positive, consistent outcomes for In.Pact DEB therapy in the femoropopliteal arteries.
IN.PACT DEEP enrolled 358 subjects with Rutherford classification stages 4, 5, and 6 from September 2009 to July 2012 at 13 sites in six European countries: Austria, Belgium, Germany, Italy, the Netherlands, and Switzerland. Patients in the study were randomized 2:1 to treatment with the In.Pact Amphirion DEB (n = 239) or PTA (n = 119). Baseline clinical, angiographic, and wound characteristics were similar across the two groups.
The study failed to meet both of its primary efficacy endpoints. On the safety endpoint, the study showed the DEB to be noninferior, but not superior, to PTA. The primary efficacy endpoints at 12 months were clinically driven target lesion revascularization (TLR) and late lumen loss for an angiographic subset. The TLR rate was 9.2% (18/196) for the DEB and 13.1% (14/107) for PTA (P = 0.291). Late lumen loss was 0.61 ± 0.78 for the DEB versus 0.62 ± 0.78 for PTA (P = 0.950). The primary safety endpoint at 6 months was a composite of all-cause mortality, major amputation, and clinically driven TLR, which was 17.7% (41/232) for the DEB versus 15.8% (18/114) for PTA.
Regarding the data, Tony Semedo, a senior vice president at Medtronic and president of the company’s Endovascular Therapies business, commented, “While the DEB outcomes in IN.PACT DEEP were disappointing, the study confirms the value of BTK angioplasty with appropriate wound care for patients with CLI and reinforces the need for our continued investment in developing solutions for this particularly challenging aspect of peripheral artery disease in the lower extremities. It will be the subject of a peer-reviewed journal article, now in development, that explores the findings in detail.”
Medtronic stated that it is actively investing in solutions for CLI. The company recently initiated the European launch of the Total Across crossing catheter, the first of three new products to address BTK CLI that it plans to introduce around the world during the next 2 years.