Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Therapeutic Efficacy of Angiogenesis Induced by Intraarterial Autologous Bone Marrow–Derived Stem Cells in Patients with Severe Peripheral Arterial Disease

Abstract

Purpose To evaluate safety and efficacy of angiogenesis induced by intraarterial autologous bone marrow–derived stem cell (BMSC) injection in patients with severe peripheral arterial disease (PAD). Materials and Methods Eighty-one patients with severe PAD (77 men), including 56 with critical limb ischemia (CLI) and 25 with severe claudication, were randomized to receive sham injection (group A) or intraarterial BMSC injection at the site of occlusion (group B). Primary endpoints included improvement in ankle–brachial index (ABI) of > 0.1 and transcutaneous pressure of oxygen (TcPO2) of > 15% at mid- and lower foot at 6 mo. Secondary endpoints included relief from rest pain, > 30% reduction in ulcer size, and reduction in major amputation in patients with CLI and > 50% improvement in pain-free walking distance in patients with severe claudication. Results Technical success was achieved in all patients, without complications. At 6 mo, group B showed more improvements in ABI of > 0.1 (35 of 41 [85.37%] vs 13 of 40 [32.50%]; P < .0001) and TcPO2 of > 15% at the midfoot (35 of 41 [85.37%] vs 17 of 40 [42.50%]; P = .0001] and lower foot (37 of 41 [90.24%] vs 19 of 40 [47.50%]; P < .0001). No patients with CLI underwent major amputation in group B, compared with 4 in group A (P = .0390). No significant difference was observed in relief from rest pain or > 30% reduction in ulcer size among patients with CLI or in > 50% improvement in pain-free walking distance among patients with severe claudication. Conclusions Intraarterial delivery of autologous BMSCs is safe and effective in the management of severe PAD.