Abstract 10077: Intra-Arterial Administration of Bone Marrow Mononuclear Cells in Patients with Critical Limb Ischemia — a Randomized-Start, Placebo-Controlled Trial (PROVASA)
Background: Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking.
Methods and Results: 40 patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intra-arterial administration of BM-MNC or placebo. After 3 months, all patients received active treatment with BM-MNC (open-label). Long-term follow-up (mean 25.3± 15 months) is available. The primary endpoint, median ABI, slightly but non significantly increased from 0.66 at baseline to 0.75 in the BM-MNC group, but remained unchanged in the placebo group (0.64 at baseline to 0.66 at 3 months). In contrast, cell therapy was associated with significantly improved ulcer healing (Ulcer area: BM-MNC: 3.2 ± 4.7 to 1.89 ± 3.5 cm2, P=0.014, versus placebo: 2.92 ±3.5 cm to 2.89 ± 4.1, P=0.5), reduced rest pain (5.2±1.8 to 2.2±1.3, P=0.009 versus placebo:4.5±2.4 to 3.9±2.6, p=0.3), and increased transcutaneous oxygen pressures TCO2 (31.6± 24 mmHg to 40.5± 23 mmHg, P=0.058, but decreased TCO2 in the placebo group (46.9 ± 11 mmHg to 39.7 ± 17 mmHg, P=0.032 within 3 months. There was no significant difference for limb salvage and amputation-free survival. Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage(r=0.8, p<0.001). Patients with thrombangitis obliterans generally responded well, whereas critically ill patients with extensive gangrene and impending amputation did not derive any benefit.
Conclusions: Intra-arterial administration of BM-MNC is safe and feasible and accelerates wound healing and reduces rest pain in patients without extensive gangrene and impending amputation. Large scale randomized trials are warranted to assess the clinical effect of repeated BM-MNC administration in patients with critical limb ischemia and stable ulcers.
- © 2010 by American Heart Association, Inc.