EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention.

C Michael Gibson, Robert P Giugliano, Robert A Kloner, Christoph Bode, Michal Tendera, András Jánosi, Bela Merkely, Jacek Godlewski, Rim Halaby, Serge Korjian, Yazan Daaboul, Anjan K Chakrabarti, Kathryn Spielman, Brandon J Neal, W Douglas Weaver

Journal: European heart journal 2018;37(16):1296-303

PMID: 26586786

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Abstract

AIMS

Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion.

METHODS AND RESULTS

EMBRACE STEMI is a multicentre, randomized, double-blind Phase 2a trial that evaluated the efficacy and safety of MTP-131 vs. placebo infused at a rate of 0.05 mg/kg/h for 1 h among first-time anterior STEMI subjects undergoing primary percutaneous coronary intervention (PCI) for a proximal or mid left anterior descending (LAD) artery occlusion. Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by creatine kinase-myocardial band (CK-MB) area under the curve (AUC) over 72 h (5785 ± 426 ng h/mL in placebo vs. 5570 ± 486 ng h/mL in MTP-131; ITALIC! P = NS). MTP-131 was not associated with an improvement in pre-specified magnetic resonance imaging, angiographic, electrocardiographic, or clinical outcomes.

CONCLUSION

Among subjects with first-time anterior STEMI due to a proximal or mid LAD lesion who undergo successful PCI, administration of MTP-131 was safe and well tolerated. Treatment with MTP-131 was not associated with a decrease in myocardial infarct size as assessed by AUC0-72 of CK-MB.

Address: PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW-459, Boston, MA 02215, USA [email protected].; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Huntington Medical Research Institutes, Pasadena, CA, USA Cardiovascular Division, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.; Cardiology and Angiology I, Heart Center, Freiburg University, Freiberg, Germany.; 3rd Department of Cardiology, School of Medicine in Katowice, Medical University of Medicine, Katowice, Poland.; Gottsegen Gyorgy National Institute of Cardiology, Budapest, Hungary.; Semmelweis University Heart Center, Budapest, Hungary.; Krakowski Szpital Specjalistyczny im. Jana Pawla II, Krakow, Poland.; Harvard Medical School, Boston, MA, USA.; Eastern Virginia Medical School, Norfolk, VA, USA.; PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW-459, Boston, MA 02215, USA.; Henry Ford Hospital, Detroit, MI, USA.

DOI: 10.1093/eurheartj/ehv597