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Clinical Trial
. 2017 Jan 20;120(2):324-331.
doi: 10.1161/CIRCRESAHA.115.308165. Epub 2016 Nov 7.

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

Arshed A Quyyumi  1 , Alejandro Vasquez  2 , Dean J Kereiakes  2 , Marc Klapholz  2 , Gary L Schaer  2 , Ahmed Abdel-Latif  2 , Stephen Frohwein  2 , Timothy D Henry  2 , Richard A Schatz  2 , Nabil Dib  2 , Catalin Toma  2 , Charles J Davidson  2 , Gregory W Barsness  2 , David M Shavelle  2 , Martin Cohen  2 , Joseph Poole  2 , Thomas Moss  2 , Pamela Hyde  2 , Anna Maria Kanakaraj  2 , Vitaly Druker  2 , Amy Chung  2 , Candice Junge  2 , Robert A Preti  2 , Robin L Smith  2 , David J Mazzo  2 , Andrew Pecora  2 , Douglas W Losordo  2
Affiliations
Clinical Trial

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

Arshed A Quyyumi et al. Circ Res. .

Abstract

Rationale: Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death.

Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI.

Methods and results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point 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 left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively.

Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364.

Keywords: cell transplantation; clinical trial; endothelial progenitor cells; heart failure; myocardial infarction.

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Figures

Figure 1
Figure 1. PRESERVE-AMI study flow diagram
†There were no deaths in the mITT treatment group *There were 3 deaths in the mITT placebo group ¥Other reasons were: AIDS, low hemoglobin values, hypotension requiring medication, re-occlusion of the infarct-related artery, pulmonary nodules, apical thrombus, CMR not being performed and subject lost prior to treatment.
Figure 2
Figure 2. Change in cardiac function and structure over time
A) Change in RTSS score from baseline to 6 months for the control (P=0.010) and CLBS10 treated (P=0.014) group. B) Change in LVEF from baseline to 6 months for the control and CLBS10 treated group (both P<0.001). No significant difference in mean RTSS or LVEF between the control vs CLBS10 treated group observed. Thick lines represent mean change in RTSS or LVEF score. Thin lines represent individual subjects. C) The mean LVEF change from baseline (±SE) in pooled treatment and cell dose subgroups was compared to control using a t-test of the means. D) Mean percent change from baseline in infarct size measured by CMR. P=NS for all comparisons.
Figure 2
Figure 2. Change in cardiac function and structure over time
A) Change in RTSS score from baseline to 6 months for the control (P=0.010) and CLBS10 treated (P=0.014) group. B) Change in LVEF from baseline to 6 months for the control and CLBS10 treated group (both P<0.001). No significant difference in mean RTSS or LVEF between the control vs CLBS10 treated group observed. Thick lines represent mean change in RTSS or LVEF score. Thin lines represent individual subjects. C) The mean LVEF change from baseline (±SE) in pooled treatment and cell dose subgroups was compared to control using a t-test of the means. D) Mean percent change from baseline in infarct size measured by CMR. P=NS for all comparisons.
Figure 2
Figure 2. Change in cardiac function and structure over time
A) Change in RTSS score from baseline to 6 months for the control (P=0.010) and CLBS10 treated (P=0.014) group. B) Change in LVEF from baseline to 6 months for the control and CLBS10 treated group (both P<0.001). No significant difference in mean RTSS or LVEF between the control vs CLBS10 treated group observed. Thick lines represent mean change in RTSS or LVEF score. Thin lines represent individual subjects. C) The mean LVEF change from baseline (±SE) in pooled treatment and cell dose subgroups was compared to control using a t-test of the means. D) Mean percent change from baseline in infarct size measured by CMR. P=NS for all comparisons.
Figure 2
Figure 2. Change in cardiac function and structure over time
A) Change in RTSS score from baseline to 6 months for the control (P=0.010) and CLBS10 treated (P=0.014) group. B) Change in LVEF from baseline to 6 months for the control and CLBS10 treated group (both P<0.001). No significant difference in mean RTSS or LVEF between the control vs CLBS10 treated group observed. Thick lines represent mean change in RTSS or LVEF score. Thin lines represent individual subjects. C) The mean LVEF change from baseline (±SE) in pooled treatment and cell dose subgroups was compared to control using a t-test of the means. D) Mean percent change from baseline in infarct size measured by CMR. P=NS for all comparisons.
Figure 3
Figure 3. Mortality and MACE in the mITT population (patients that received and infusion of CD34 cells or control)
Kaplan-Meier plots of the probability of A) survival for the CLBS10 and control treated subjects. P-values reflect a log-rank test of treatment vs control. B) Percentage of subjects experiencing MACE during the post-infusion follow-up period (median follow-up: 12 months).
Figure 3
Figure 3. Mortality and MACE in the mITT population (patients that received and infusion of CD34 cells or control)
Kaplan-Meier plots of the probability of A) survival for the CLBS10 and control treated subjects. P-values reflect a log-rank test of treatment vs control. B) Percentage of subjects experiencing MACE during the post-infusion follow-up period (median follow-up: 12 months).
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