Selected CD133+ Progenitor Cells to Promote Angiogenesis in Patients with Refractory Angina: The Final Results of the PROGENITOR Randomized Trial.

Abstract

Rationale: Refractory angina (RA) constitutes a clinical problem.

Objective: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133+cells to foster angiogenesis in patients with RA.

Methods and Results: in this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte-colony-stimulating factor, underwent an apheresis and NOGA mapping and were randomized to receive treatment with CD133+cells or no treatment. The primary endpoint was the safety of transendocardial injection of CD133+cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6-month. Secondary endpoints analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6-month, 1 patient in each group suffered ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters, however, the comparison within groups showed: a significant improvement in the number of angina episodes/per month (median-absolute difference (mAD):-8.5(95%CI, -15.0;-4-0) and in angina functional class in the treatment arm but not in the control group. At 6-months, only one SPECT parameter: Summed Score improved significantly in the treatment group: at rest and at stress:(mAD:-1.0(95%CI,-1.9;-0.1) but not in the control arm.

Conclusions: Our findings support feasibility and safety of transendocardial injection of CD133+cells in patients with RA. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.