Cardiac Function Improvement and Bone Marrow Response -: Outcome Analysis of the Randomized PERFECT Phase III Clinical Trial of Intramyocardial CD133+ Application After Myocardial Infarction

EBioMedicine. 2017 Aug:22:208-224. doi: 10.1016/j.ebiom.2017.07.022. Epub 2017 Jul 29.


Objective: The phase III clinical trial PERFECT was designed to assess clinical safety and efficacy of intramyocardial CD133+ bone marrow stem cell treatment combined with CABG for induction of cardiac repair.

Design: Multicentre, double-blinded, randomised placebo controlled trial.

Setting: The study was conducted across six centres in Germany October 2009 through March 2016 and stopped due slow recruitment after positive interim analysis in March 2015.

Participants: Post-infarction patients with chronic ischemia and reduced LVEF (25-50%).

Interventions: Eighty-two patients were randomised to two groups receiving intramyocardial application of 5ml placebo or a suspension of 0.5-5×106 CD133+.

Outcome: Primary endpoint was delta (∆) LVEF at 180days (d) compared to baseline measured in MRI.

Findings (prespecified): Safety (n=77): 180d survival was 100%, MACE n=2, SAE n=49, without difference between placebo and CD133+. Efficacy (n=58): The LVEF improved from baseline LVEF 33.5% by +9.6% at 180d, p=0.001 (n=58). Treatment groups were not different in ∆LVEF (ANCOVA: Placebo +8.8% vs. CD133+ +10.4%, ∆CD133+vs placebo +2.6%, p=0.4).

Findings (post hoc): Responders (R) classified by ∆LVEF≥5% after 180d were 60% of the patients (35/58) in both treatment groups. ∆LVEF in ANCOVA was +17.1% in (R) vs. non-responders (NR) (∆LVEF 0%, n=23). NR were characterized by a preoperative response signature in peripheral blood with reduced CD133+ EPC (RvsNR: p=0.005) and thrombocytes (p=0.004) in contrast to increased Erythropoeitin (p=0.02), and SH2B3 mRNA expression (p=0.073). Actuarial computed mean survival time was 76.9±3.32months (R) vs. +72.3±5.0months (NR), HR 0.3 [Cl 0.07-1.2]; p=0.067.Using a machine learning 20 biomarker response parameters were identified allowing preoperative discrimination with an accuracy of 80% (R) and 84% (NR) after 10-fold cross-validation.

Interpretation: The PERFECT trial analysis demonstrates that the regulation of induced cardiac repair is linked to the circulating pool of CD133+ EPC and thrombocytes, associated with SH2B3 gene expression. Based on these findings, responders to cardiac functional improvement may be identified by a peripheral blood biomarker signature.

Trial registration: ClinicalTrials.govNCT00950274.

Keywords: Angiogenesis; CD133(+); CD34(+); Cardiac repair; Cardiac stem cell therapy; Endothelial progenitor cell (EPC); Lnk adaptor; Randomised double-blinded phase III multicentre trial; SH2B3.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • AC133 Antigen / metabolism*
  • Adult
  • Aged
  • Bone Marrow Cells / immunology*
  • Bone Marrow Transplantation*
  • Double-Blind Method
  • Female
  • Humans
  • Machine Learning
  • Male
  • Middle Aged
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / therapy*
  • Survival Analysis
  • Treatment Outcome
  • Ventricular Function, Left


  • AC133 Antigen
  • PROM1 protein, human

Associated data