Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial.

Autor:	Makkar RR; Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA., Kereiakes DJ; The Christ Hospital, Cincinnati, 2139 Auburn Ave, Cincinnati, OH 45219, USA., Aguirre F; Prairie/St. Johns Hospital, Springfield, 800 E Carpenter St, Springfield, IL 62769, USA., Kowalchuk G; Sanger Heart & Vascular, Charlotte, 1001 Blythe Blvd Ste 300, Charlotte, NC 28203, USA., Chakravarty T; Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA., Malliaras K; University of Athens, 17 Agiou Thoma street, 11527, Athens, Greece., Francis GS; University of Minnesota Heart Care, Minneapolis, 6405 France Ave S, Edina, MN 55435, USA., Povsic TJ; Duke University Hospital, Durham, 2301 Erwin Rd, Durham, NC 27710, USA., Schatz R; Scripps Green Hospital, 10666 N Torrey Pines Rd, La Jolla, CA 92037, USA., Traverse JH; Minneapolis Heart Institute Foundation, 920 E 28th St Ste 100, Minneapolis, MN 55407, USA., Pogoda JM; 10Capricor Therapeutics, Los Angeles, 8840 Wilshire Blvd Ste 2, Beverly Hills, CA 90211, USA., Smith RR; 10Capricor Therapeutics, Los Angeles, 8840 Wilshire Blvd Ste 2, Beverly Hills, CA 90211, USA., Marbán L; 10Capricor Therapeutics, Los Angeles, 8840 Wilshire Blvd Ste 2, Beverly Hills, CA 90211, USA., Ascheim DD; 10Capricor Therapeutics, Los Angeles, 8840 Wilshire Blvd Ste 2, Beverly Hills, CA 90211, USA., Ostovaneh MR; J ohns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA., Lima JAC; J ohns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA., DeMaria A; University of California San Diego Medical Center, 200 W. Arbor Drive, San Diego, CA 92103, USA., Marbán E; Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA., Henry TD; Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2020 Sep 21; Vol. 41 (36), pp. 3451-3458.
DOI:	10.1093/eurheartj/ehaa541
Abstrakt:	Aims: Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and Results: We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion: Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. Trial Registration: Clinicaltrials.gov identifier: NCT01458405. (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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