Abstract 13678: A Phase II Clinical Trial to Explore Various Endpoints and Their Timings for GCSF-Mobilized CD34+ Cell Therapy in No-Option Patients with Critical Limb Ischemia
Background: Our phase I/IIa clinical trial revealed the safety, feasibility and potential efficacy of GCSF-mobilized CD34+ cells at week 4 and 12 post cell therapy in patients with no-option critical limb ischemia (CLI).
Methods: A phase II trial was conducted to explore various endpoints and their timings suitable for the future pivotal study. No-option CLI patients (N=11) by atherosclerotic peripheral arterial disease or Buerger’s disease underwent intramuscular transplantation of GCSF-mobilized CD34+ cells isolated by a magnetic sorting system, Isolex. CLI-free ratio based on Rutherford’s category, ischemic rest pain scales, and physiological parameters of limb perfusion and exercise tolerance were evaluated at week 2, 4, 8, 12, 24, 36 and 52 post cell therapy.
Results: No patients died, and 1 patient underwent major amputation until week 52. Rutherford’s category significantly improved from week 24 (3.0[2.0~5.0]) vs baseline (4.0[4.0~5.0]) (P<0.01). CLI-free ratio serially increased and peaked (85.7%) at week 36. VAS (2.1±2.7 vs 5.4±2.3, P<0.0001), Wong-Baker FACES pain rating scale (1.0[1.0~3.0] vs 3.0[2.0~4.0], P<0.001) and Rest Pain Scale (1.0[1.0~3.0] vs 2.0[2.0~4.0], P<0.05) significantly improved from week 2 vs baseline. Skin perfusion pressure (29.2±6.4 vs 23.8±5.6 mmHg, P<0.05), transcutaneous partial oxygen pressure (35.4±15.4 vs 22.9±15.8 mmHg, P<0.05) and pain-free walking distance (204.4±136.6 vs 93.9±68.4 m, P<0.01) improved from week 2, total walking distance from week 8 (304.1±95.5 vs 204.5±148.4 m, P<0.05) and toe brachial pressure index from week 12 (0.3±0.1 vs 0.2±0.1, P<0.05) vs baseline. These parameters peaked at week 36 or 52. Serial change in Rutherford’s category correlated with that in Rest Pain Scale (P<0.05), but not any physiological parameters.
Conclusions: Ischemic rest pain scales and physiological parameters may improve early after the cell therapy, then peaked later accompanied with recovery from CLI. In addition to the true endpoints such as amputation-free survival, Rutherford’s category and CLI-free ratio at week 24 or later may be suitable surrogate endpoints in the phase III trial. Physiological parameters would be also evaluated independently of such clinical endpoints for ischemia severity.
- © 2012 by American Heart Association, Inc.