A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute anterior myocardial infarction (n=100). Intervention: Intracoronary autologous bone marrow-derived cells (BMC) vs. Matching placebo (10 mL sterile NaCl 0.9% with 33 μL autologous whole bone marrow). Primary outcome: Absolute change in global left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging (MD 2.2, 95% CI -0.5 to 5.0, p=0.10).

Q: What does this research mean for the field?

Intracoronary infusion of autologous bone marrow-derived cells within 24 hours of primary percutaneous coronary intervention for acute myocardial infarction yields a small, non-significant improvement in left ventricular ejection fraction but significantly improves myocardial salvage. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Fizzah Choudry; Stephen Hamshere; Natalie Saunders; Jessry Veerapen; Katrine Bavnbek; Charles Knight; Denis Pellerin; Didier Locca; Mark Westwood; Roby Rakhit; Tom Crake; Jens Kastrup; Mahesh Parmar; Samir Agrawal; Daniel A. Jones; John Martin; Anthony Mathur

doi:10.1093/eurheartj/ehv493

September 23, 2015European Heart JournalOpen Access

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

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Key result

Early intracoronary infusion of autologous bone marrow-derived cells following primary PCI resulted in a small, non-significant 2.2% absolute improvement in LVEF at 1 year compared with placebo.

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Why the study?

Intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-AMI may improve LV function, but earlier time points within 24 hours of reperfusion had not been evaluated.

Does early intracoronary infusion of autologous bone marrow-derived cells within 24 hours of primary PCI improve left ventricular ejection fraction in patients with anterior acute myocardial infarction?

Key Points

To determine whether intracoronary autologous bone marrow-derived cell infusion delivered within 24 hours of successful reperfusion improves left ventricular function in acute myocardial infarction.
Multicentre, phase II, randomized, double-blind, placebo-controlled trial across five recruitment centres enrolling 100 patients with anterior acute myocardial infarction and regional wall motion abnormality.
Participants were randomized 1:1 to receive an intracoronary infusion of autologous bone marrow-derived cells (n=55) or placebo (n=45) within 24 hours of successful primary percutaneous coronary intervention.
The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to 1 year evaluated by advanced cardiac imaging (cardiac magnetic resonance or CT).
At 1 year, LVEF increased from baseline by 5.1% in the cell therapy group (47.5 ± 9.2% to 52.6 ± 10.5%; P < 0.0001) and by 2.8% in the placebo group (49.2 ± 9.6% to 52.0 ± 9.1%; P = 0.0019), yielding a non-significant between-group difference of 2.2% (95% CI: -0.5 to 5.0; P = 0.10).
Myocardial salvage index at Day 3 was significantly greater in the cell therapy group compared with placebo (between-group difference 0.1%; 95% CI: 0.0-0.20; P = 0.048).
Major adverse cardiac events were rare and did not differ significantly between groups (P = 0.95), with one death in the cell group and none in the placebo group.

Study Design

Type

RCT (n=100)

Blinding

Double-blind

Randomization

1:1 block randomization

Multicenter

Yes

Structured PICO

Does early intracoronary infusion of autologous bone marrow-derived cells within 24 hours of primary PCI improve left ventricular ejection fraction in patients with anterior acute myocardial infarction?

P

Population

100 adult patients (mean age 56.5, 13% female) with acute anterior myocardial infarction and significant regional wall motion abnormality who underwent successful primary percutaneous coronary intervention within 24 hours, followed for 1 year.

I

Intervention

Autologous bone marrow-derived cells (BMC) infused intracoronarily in three fractions during stop flow conditions within 24 hours of successful primary percutaneous intervention.

C

Comparator

Matching placebo (10 mL sterile NaCl 0.9% with 33 μL autologous whole bone marrow to match color) infused intracoronarily.

O

Outcome

Absolute change in global left ventricular ejection fraction (LVEF) assessed by advanced cardiac imaging (CMR or CT) at 1 year compared with baseline.surrogate

Main Result

Mean Difference: 2.2 (95% CI -0.5–5)

Absolute Event Rate: 5.1% vs 2.8%

p-value: p=0.10

Early intracoronary infusion of autologous bone marrow-derived cells within 24 hours of successful primary PCI is safe but does not significantly improve left ventricular ejection fraction at 1 year compared to placebo.

Limitations

Small sample size based on early phase II trials
Relatively high ejection fractions at baseline scan
LVEF used as a surrogate marker for the primary endpoint instead of hard clinical outcomes
No comparable imaging performed at the time of infusion to definitively attribute day 3 differences in infarct size to the treatment
Small sample size limits power to detect a significant effect
Relatively high baseline ejection fractions in the enrolled population
Use of LVEF as a surrogate endpoint rather than hard clinical outcomes
Lack of baseline imaging directly at the time of cell infusion

Implication

Fails to show significant LVEF benefit from early bone marrow cell infusion post-PCI; challenges prior positive signals and directs research to alternative strategies.

Abstract

AIMS: Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. METHODS AND RESULTS: A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0.048). Major adverse events were rare in both treatment groups. CONCLUSION: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.

Discussion

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Cite This Study

Choudry et al. (2015) conducted an RCT in Acute anterior myocardial infarction (n=100). Intracoronary autologous bone marrow-derived cells (BMC) vs. Matching placebo (10 mL sterile NaCl 0.9% with 33 μL autologous whole bone marrow) was evaluated on Absolute change in global left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging (MD 2.2, 95% CI -0.5 to 5.0, p=0.10). Early intracoronary infusion of autologous bone marrow-derived cells following primary PCI resulted in a small, non-significant 2.2% absolute improvement in LVEF at 1 year compared with placebo.

synapsesocial.com/papers/6a3017f324c2c42f24de9f5c https://doi.org/10.1093/eurheartj/ehv493

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A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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