PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients with Left Ventricular Dysfunction Post STEMI
Rationale: Despite direct immediate intervention and therapy, ST segment Elevation Myocardial Infarction (STEMI) victims remain at risk for infarct expansion, heart failure, re-infarction, repeat revascularization and death.
Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction (LVD) post-STEMI.
Methods and Results: Patients who underwent successful stenting for STEMI and had LVD (ejection fraction [EF] ≤48%) ≥4 days post-stent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (A) autologous CD34+ cells (minimum 10M±20% cells; N=78) or (B) diluent alone (N=83), via intracoronary infusion. The primary safety endpoint was adverse events (AEs), serious AEs (SAEs) and major adverse cardiac event (MACE). The primary efficacy endpoint was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (p<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose dependent effect was observed in the change in LVEF and infarct size, and the duration of time subjects were alive and out of hospital (p=0.05). At one year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively.
Conclusions: This Phase 2, randomized, double-blind, placebo-controlled trial (PreSERVE-AMI) represents the largest study of cell-based therapy for STEMI completed in US and provides evidence supporting safety and potential efficacy in patients with LVD post STEMI who are at risk for death and major morbidity. [ClinicalTrials.gov identifier: NCT01495364]
- CD34+ cells
- myocardial ischemia
- cell transplantation
- ST-segment elevation myocardial infarction
- clinical trial
- stem cell
- endothelial progenitor cells
- Received December 14, 2015.
- Revision received October 4, 2016.
- Accepted November 7, 2016.