Abstract 16920: Randomized, Double-Blind, Placebo Controlled Trial of Autologous CD34+ Cell Therapy for Critical Limb Ischemia: 1 Year Results
Background: Critical limb ischemia (CLI) results in >100,000 amputations/yr in US alone. Pre-clinical studies provided evidence that human CD34+ cells(CD34) can stimulate new vessel formation in ischemic limbs, improving perfusion and salvaging function.
Methods: A phase IIa randomized, double-blind, placebo-controlled clinical trial of autologous CD34+ cell therapy was performed in pts in Rutherford class 4 and 5 CLI at 18 centers in US. 3 treatment groups: placebo, low (1×10^5 CD34/kg body wt) and high dose (1×10^6 CD34/kg). All pts underwent mobilization with GCSF 5 mcg/kg/day SC for 5 d, followed by apheresis on d5 to collect mononuclear cells. On d 6 CD34 were purified using Isolex 300i device. After lot release testing, CD34 were injected IM at 8 locations in the ischemic limb. Placebo injections consisted of identical volumes of the diluent only.
Results: A total of 28 pts were randomized and completed the injection procedure and 24 completed the 6 mo evaluation. Mean age of pts was 66.6±13.0, 9 female and 19 male. At 6 mo 75%(9/12) of placebo treated pts had experienced a minor or major amputation vs. 43%(3/7) of low dose CD34 treated pts and 22%(2/9) of high dose CD34 treated pts (p=0.02 for control vs. combined treatment groups). The median time to the first amputation in the control group and combined treatment groups were 110 days and >183 days respectively (control vs. high dose p=0.011, log rank test). Major amputation had occurred in 50% of controls, 43% of low dose and 22% of high dose CD34 treated pts. The full 12 month data analysis will be completed in September 2010 and will be presented.
Conclusions: A single administration of unmodified, autologous CD34 cell therapy was associated with significantly reduced rates of amputation in subjects with Rutherford class 4 and 5 critical limb ischemia. Ongoing analysis will examine additional endpoints, and will determine sample size and suitability of this therapy for a phase III study in patients with critical limb ischemia.
- © 2010 by American Heart Association, Inc.