Eric T. Choi MD¹, Patrick Geraghty MD², Christine Cooke MD², Kenneth Schechtman MD², Daniel Link MD², Christopher M. Chambers MD³, Ravi K. Veeraswamy MD^4
1Surgery, Temple University, Philadelphia, PA; ²Washington University, St. Louis, MO; ³Spectrum Health , Grand Rapids, MI;  ⁴Emory University, Atlanta, GA

OBJECTIVES: Currently, there is no proven effective non-invasive treatment for critical limb ischemia (CLI). We hypothesized that mobilization of circulating angiogenic cells into the blood by SQ injections of G-CSF may stimulate angiogenesis and result in a sustained improvement in blood flow in the lower extremities of patients with CLI.

METHODS: Highest at risk population for impending leg amputation was identified as CLI patients (Rutherford category 5 or 6) with no surgical or endovascular revascularization options. After informed consent, all subjects were randomized (1:1) in a double-blinded fashion to treatment with daily SQ injection of G-CSF (5 μg/kg/day) or placebo (saline) for 10 days. The treatment failure was defined as a end point of major leg amputation at 12 months.

RESULTS: We enrolled 28 subjects with 24 completing the 12-month follow-up. Four subjects were disqualified due inability to complete the 10-day treatment. There were no significant differences between treatment and control groups in any of the demographic parameters. At 12 months, the major amputation rates were 50% (6 out of 12) for G-CSF group and 83.3% (10 out of 12) for control group (log-rank test, P=0.188). However, after 4 months, none of 6 remaining G-CSF treated subjects required a major amputation while 3 out of 5 remaining controlled subjects went on to have a major amputation suggesting that minimal effective duration of therapeutic angiogenesis from G-CSF treatment is 4 months. No adverse effects attributable to SQ injection of G-CSF were reported.

CONCLUSIONS: We performed the first randomized, placebo-controlled, double-blinded study of C-GSF–induced angiogenic cell mobilization to treat no-option CLI patients in the US. This analysis was designed to demonstrate feasibility and safety of G-CSF treatment, and the preliminary data support a larger clinical trial to determine the effectiveness of G-CSF in CLI patients.

AUTHOR DISCLOSURES: E. Choi, Financial disclosures; Research Grants: Novartis; Honorarium: Cook Medical; P. Geraghty, Nothing to disclose; C. Chambers, Nothing to disclose; R. Veeraswamy, Nothing to disclose; C. Cooke, Nothing to disclose; K. Schechtman, Nothing to disclose; D. Link, Nothing to disclose.

Posted April 2012