Effects of Transendocardial 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

Circ Res. 2017 Feb 17;120(4):670-680. doi: 10.1161/CIRCRESAHA.116.309009. Epub 2016 Nov 30.

Abstract

Rationale: New therapies for refractory angina are needed.

Objective: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina.

Methods and results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], P=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months.

Conclusion: Transendocardial 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 versus placebo.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Keywords: angina pectoris; angiogenesis; bone marrow; cell therapy; stem cell.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • AC133 Antigen / administration & dosage*
  • Aged
  • Angina Pectoris / diagnostic imaging*
  • Angina Pectoris / epidemiology
  • Angina Pectoris / therapy*
  • Bone Marrow Cells / physiology
  • Bone Marrow Transplantation / methods*
  • Canada / epidemiology
  • Double-Blind Method
  • Endocardium / cytology
  • Endocardium / physiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Prospective Studies
  • Tomography, Emission-Computed, Single-Photon / methods
  • Transplantation, Autologous / methods
  • Treatment Outcome
  • Ventricular Function, Left / physiology*

Substances

  • AC133 Antigen
  • PROM1 protein, human

Associated data

  • ClinicalTrials.gov/NCT01660581