DRUG
Bendavia (MTP-131)
0.05 mg/kg/hr
Status
Completed
Phase
Phase 2
Enrollment
300
Locations
30
Results
Posted
Publications
2
Study summary
The EMBRACE-STEMI trial was a Phase 2a prospective, multicenter, multinational randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and efficacy of IV administered elamipretide (also known as MTP-131, or Bendavia) on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall ST-segment elevation myocardial infarction (STEMI).
The EMBRACE-STEMI trial was a Phase 2a prospective, multicenter, multinational randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and efficacy of IV administered elamipretide on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall STEMI. Patients were randomized to receive either an infusion of elamipretide at 0.05 mg/kg/hr or an identically appearing placebo administered as an IV infusion at 60 mL/hr. The infusion began at least 15 minutes but no more than 1 hour prior to the anticipated reperfusion event and continued through approximately 1 hour following re-establishment of blood flow through the culprit vessel. The reduction of reperfusion injury, or infarct size, was estimated using the area under the curve (AUC) of the serum creatine kinase (CK) isoenzyme, as well as using magnetic resonance imaging (MRI) performed on the Day 4±1 and on Day 30±7 (both MRI assessments measured infarct size and the ratio of infarct size to myocardial mass). The analyses of cardiac MRI data were performed for both the primary endpoint population and also in all patients who had adequate Day 4/Day 30 cardiac MRI studies. After completion of the percutaneous coronary intervention (PCI) and stenting, patients received standard medical treatment.
Interventions
DRUG
0.05 mg/kg/hr
DRUG
Identically appearing placebo
Timeline
First posted
Apr 6, 2012
Study start
Apr 2012
Primary completion
Nov 2014
Study completion
Feb 2015
Results posted
Jun 11, 2020
Registry updated
Jun 11, 2020
Outcomes
Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
Time frame · The initial 24 and 72 hours post-percutaneous coronary intervention (PCI)
Infarct size as measured by the AUC of serum CK-MB at 24 and 72 hours post-PCI
AUC of Troponin 1 Enzyme
Time frame · Initial 24 and 72 hours post-PCI
Infarct size as calculated by the AUC of Troponin I Enzyme over the initial 24 and 72 hours post-PCI
Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass
Time frame · Day 30 + 7
Cardiac infarct size calculated as the ratio of volume of infarcted myocardium to left ventricular mass at Day 30 as measured by MRI.
Thrombosis in Myocardial Infarction (TIMI) Perfusion Grade Flow at Completion of PCI
Time frame · Initiation to Completion of PCI, no longer than 4 hours
TIMI perfusion grade flow at completion of PCI will be categorized as 0,1, or 1.5, 2 or 2.5, 3, and treated as ordinal data, where higher score means better perfusion and lower score means worse perfusion and worse outcome.
Corrected TIMI Frame Count
Time frame · Completion of PCI, no longer than 4 hours
Corrected TIMI Frame Count at Completion of PCI as captured by angiogram and analyzed as a continuous variable.
ST-Segmented Elevation From Pre-PCI to 24 Hours Post-PCI and Presence of ST-Segmented Resolution
Time frame · pre-PCI to 24 hours post-PCI
ST-Segmented Elevation from pre-PCI to 24 hours post-PCI and Presence of ST-Segmented Resolution by ECG
Change in Serum Creatinine From Baseline
Time frame · Day 30 +7
Change in serum creatinine, from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline
Time frame · Day 30 +/- 7
Change in eGFR from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Cystatin C Change From Baseline
Time frame · Day 30 + 7
Change in Cystatin C from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Blood Urea Nitrogen (BUN) Change From Baseline
Time frame · Baseline to Day 30
Blood Urea Nitrogen (BUN) Change from baseline (prior to study drug administration) to Day 30 + 7 post-PCI
Number and Percent of Grade 1 Episode of Contrast-Induced Nephropathy Post-PCI
Time frame · Baseline to 48 hours post PCI or MRI
Number of Participants with Grade 1 Episode of Contrast-Induced Nephropathy within 48 hours of initial PCI or MRI, based on lab data.
Eligibility
Inclusion Criteria: * Age ≥18 and \<85 years * The patient presents with first-time acute, anterior wall STEMI scheduled to undergo primary PCI and stenting. * The patient has symptoms of cardiac ischemia of ≥10 minutes. * The patient must demonstrate an anterior wall STEMI with \>0.1 millivolt (mV) ST-segment elevation in at least two contiguous precordial leads (i.e., V1-V4) or presumed new left bundle branch block. * The time from onset of symptoms of cardiac ischemia to the anticipated time of initial PCI balloon inflation does not exceed four (4) hours and it is anticipated that the door-to-balloon time will be \<2 hours. * For female patients of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the follow-up visit. Female patients of childbearing potential must have a negative serum pregnancy test prior to entry into the study. * Female patients not of childbearing potential (i.e. female patients who are postmenopausal since last regular menses, or have been surgically sterilized at least 1 year prior to screening visit) are eligible to enter the study. * For male patients with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the post-study medical. * Written informed consent obtained that strictly adheres to the written guidelines from the local Institutional Review Board (IRB)/ Ethical Committee (EC). Exclusion Criteria * Cardiogenic shock or maximal systolic blood pressure (BP) \<80 mm Hg after fluid and/or vasopressor resuscitation on at least two consecutive readings. * Ongoing vasopressor support. * Uncontrolled hypertension defined as a systolic BP \>180 mm Hg or a diastolic BP \>110 mm Hg on at least two consecutive readings. * Cardiac arrest or arrhythmia requiring prolonged (\>5 minutes) chest compressions/ cardiopulmonary resuscitation (CPR). * Prior coronary artery bypass graft surgery (CABG). * Prior myocardial infarction (MI). * Implantable cardioverter-defibrillator (ICD) or permanent pacemaker (PPM) unless known to be MRI safe. The presence of an MRI-compatible pacemaker or other MRI-compatible hardware will not be a contraindication to participation in this trial. * Known left ventricular ejection fraction \<30% prior to the qualifying infarct. * History of clinically significant hepatic disturbance or chronic renal impairment at the time of admission. * Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the last 30 days. * Any known disorder that is associated with immunologic dysfunction (e.g., cancer, lymphoma, a positive serologic test for the human immunodeficiency virus, or hepatitis) more recently than 6 months before presentation or the administration of immunosuppressive drugs within 10 days of the STEMI at doses expected to be associated with immunosuppression including high dose steroids (\>2.5 mg/d hydrocortisone or equal potency of synthetic steroids), tumor necrosis factor-alpha (TNF-α) blockers or methotrexate/azathioprine. * Any condition that, in the Investigator's opinion, would prevent adherence to the requirements of the protocol including language barrier or current alcohol or drug abuse. * Contraindications (including claustrophobia) to cardiac MRI at study entry. * Participation in an investigational drug or device study within the 30 days prior to enrollment into the EMBRACE-STEMI Trial or anticipated within the next 4 days. * Female patients who are pregnant or breastfeeding during the study or intend to within 30 days of receiving study drug.
Study locations
Germany · Hungary · Poland · United States. Showing up to 24 locations stored in the fast local snapshot.
Advanced Medical Research Center
Port Orange, Florida, United States
Henry Ford Hospital
Detroit, Michigan, United States
Creighton Cardiac Center
Omaha, Nebraska, United States
Universitätsmedizin Berlin, Charité Campus Benjamin Franklin
Berlin, Germany
Staedtische Kliniken Bielefeld
Bielefeld, Germany
Marienhaus Klinikum Eifel
Bitburg, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Germany
Klinikum Herford
Herford, Germany
Robert-Bosch-Krankenhaus Kardiologie
Stuttgart, Germany
Helios Klinikum Wuppertal, Herzzentrum Elberfeld
Wuppertal, Germany
Gottsegen Gyorgy Orszagos Kardiologiai Intezet
Budapest, Hungary
Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68
Budapest, Hungary
Honvédkórház-Állami Egészségügyi Központ
Budapest, Hungary
PTE Klinikai Központ Szívgyógyászati Klinika
Pécs, Hungary
Szent György Kórház, II. Belgyógyászati Osztály
Székesfehérvár, Hungary
Zala Megyei Kórház, Kardiológiai Osztály, Zrínyi Miklós út 1.
Zalaegerszeg, Hungary
Medical University of Bialystok
Bialystok, Poland
SPSK Nr 7 Klaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszka Gieca, III Oddzial Kardiologii, Zklad Kardiologii Inwazjnejul, Ziolowa 45-47
Katowice, Poland
SPSK Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszaka Gieca, I Oddzial Kardiologii, ul. Ziolowa 45-47
Katowice, Poland
Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii
Kielce, Poland
Krakowski Szpital Specjalistyczny im. Jana Pwla II, Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kariologii Interwencyjnej
Krakow, Poland
Wojewodzki Specjalistyczny Szpital im WI. Bieganskiego, II Katedra i Klinika Kardiologii Uniwersytetu Medycznego w Lodzi, Pracownia Kardiologii Inwazyinej, ul. Kniaziewicza 1/5
Lodz, Poland
SP ZOZ Wojewodzkie Centrum Medyczne, Zaklad Diagnostyki Obrazowej, AI. W. Witosa 26
Opole, Poland
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii
Oświęcim, Poland
Publications
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