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

• Published in: European Heart Journal Vol. 37; no. 16; pp. 1296.1 - 1303
• Main Authors: Gibson, C. Michael, Giugliano, Robert P., Kloner, Robert A., Bode, Christoph, Tendera, Michal, Jánosi, András, Merkely, Bela, Godlewski, Jacek, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Chakrabarti, Anjan K., Spielman, Kathryn, Neal, Brandon J., Weaver, W. Douglas
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 21.04.2016
• Subjects: Double-Blind Method; Humans; Oligopeptides; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; MTP-131; STEMI; Mitochondrial dysfunction; Reperfusion injury; PCI
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehv597

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. 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. 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.