Effects of Trans-Endocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

Rationale: New therapies for refractory angina are needed. Objective: Assessment of trans-endocardial delivery of bone marrow (BM) CD133 + cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent CCS II-IV angina despite optimal medical therapy, ≥ one myocardial segment with inducible ischemia in Tc-99m SPECT who underwent BM biopsy and were allocated to cells (n=16) or placebo (n=15). Primary endpoint was absolute change in myocardial ischemia by SPECT. Secondary end-points were LV function and volumes by MRI and angina severity. After 4 months there were no significant differences in extent of inducible ischemia between groups [summed difference score (SDS) mean (±SD) 2.60 (2.6) vs. 3.63 (3.6), p=0.52; total perfusion deficit 3.60 (3.6) vs 5.01 (4.3), p=0.32]; absolute changes of SDS [-1.38 (5.2) vs. -0.73 (1.9), p=0.65 and total perfusion deficit -1.33 (3.3) vs. -2.19 (6.6), p=0.65]. There was a significant reduction of LV volumes [ESV: -4.3 (11.3) vs. 7.4 (11.8), p=.02; EDV: -9.1 (14.9) vs. 7.4 (15.8), p=.02] and no significant change of LVEF in the cell group. There was no difference in number patients showing improvement of ≥ one CCS class after one (41.7% vs. 58.3%, p=0.68), four (50% vs. 33.3%, p=0.63), six (70% vs. 50.0%, p=0.42) and twelve months (55.6% vs. 81.8%, p=0.33) and use of nitrates after 12 months. Conclusions: Trans-endocardial CD133 + cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina vs. placebo. Clinical Trial Registration: NCT01660581.