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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
300
0.05 mg/kg/hr
Identically appearing placebo
Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
Infarct size as measured by the AUC of serum CK-MB at 24 and 72 hours post-PCI
Time frame: The initial 24 and 72 hours post-percutaneous coronary intervention (PCI)
AUC of Troponin 1 Enzyme
Infarct size as calculated by the AUC of Troponin I Enzyme over the initial 24 and 72 hours post-PCI
Time frame: Initial 24 and 72 hours post-PCI
Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass
Cardiac infarct size calculated as the ratio of volume of infarcted myocardium to left ventricular mass at Day 30 as measured by MRI.
Time frame: Day 30 + 7
Thrombosis in Myocardial Infarction (TIMI) Perfusion Grade Flow at Completion of PCI
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.
Time frame: Initiation to Completion of PCI, no longer than 4 hours
Corrected TIMI Frame Count
Corrected TIMI Frame Count at Completion of PCI as captured by angiogram and analyzed as a continuous variable.
Time frame: Completion of PCI, no longer than 4 hours
ST-Segmented Elevation From Pre-PCI to 24 Hours Post-PCI and Presence of ST-Segmented Resolution
ST-Segmented Elevation from pre-PCI to 24 hours post-PCI and Presence of ST-Segmented Resolution by ECG
Time frame: pre-PCI to 24 hours post-PCI
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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
...and 20 more locations
Change in Serum Creatinine From Baseline
Change in serum creatinine, from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Time frame: Day 30 +7
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline
Change in eGFR from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Time frame: Day 30 +/- 7
Cystatin C Change From Baseline
Change in Cystatin C from baseline (prior to study drug administration) to Day 30 +7 post-PCI
Time frame: Day 30 + 7
Blood Urea Nitrogen (BUN) Change From Baseline
Blood Urea Nitrogen (BUN) Change from baseline (prior to study drug administration) to Day 30 + 7 post-PCI
Time frame: Baseline to Day 30
Number and Percent of Grade 1 Episode of Contrast-Induced Nephropathy Post-PCI
Number of Participants with Grade 1 Episode of Contrast-Induced Nephropathy within 48 hours of initial PCI or MRI, based on lab data.
Time frame: Baseline to 48 hours post PCI or MRI
Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation
Number and percent of participants with Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation Requiring Medical Intervention
Time frame: Baseline up to 1 hour post-PCI
Immediate Myocardial Complications: Mechanical Complications
Number and Percent of Participants with Immediate Myocardial Complications: Mechanical Complications: (Free wall Rupture, Ventricular Septal Defect, Ischemic Mitral Regurgitation)
Time frame: Baseline up to 1 hour post-PCI
Emergency Use of Medications During PCI Procedure
Emergency Use of Nitroprusside, Calcium Channel Blocker, Adenosine Administration During the PCI Procedure
Time frame: Initiation to Completion of PCI, no longer than 4 hours
ProB-type Natriuretic Peptide (NT-proBNP) Change From Baseline to Day 30
NT-proBNP: Change from baseline to Day 30 +7 (Laboratory marker for chronic heart failure (CHF) and systemic inflammation.)
Time frame: Baseline to Day 30
High Sensitivity C-Reactive Protein (hsCRP): Change From Baseline to Day 30
High Sensitivity C-Reactive Protein (hsCRP): Change from baseline to Day 30 +7 (Laboratory Marker for CHF and Systemic Inflammation)
Time frame: Baseline to Day 30
Left Ventricular (LV) Ejection Fraction (%)
Difference in Left Ventricular (LV) Ejection Fraction (%) from Day 4 To Day 30
Time frame: Day 4 to Day 30
Difference Between Left Ventricular End Diastolic Volume, Corrected
Difference between Left Ventricular End Diastolic Volume Corrected for Body Surface Area between Day 4 and Day 30
Time frame: Day 4 and Day 30
Difference Between Left Ventricular End Systolic Volume, Corrected
Difference between Left Ventricular End Systolic Volume Corrected for Body Surface Area from Day 4 and Day 30
Time frame: Day 4 and Day 30
Chronic Heart Failure
Number and Percentage of Patients with Clinical Events: Chronic Heart Failure beginning within 24 hours after PCI but within the duration of the index hospitalization (Subjects with CHF started within 24 hours after the last balloon deflation while the patient was still in the hospital {including patients who had missing discharge date}).
Time frame: Within 24 hours after PCI