Evaluation of Myocardial Effects of MTP-131 for Reducing Reperfusion Injury in Patients With Acute Coronary Events
Condition: Reperfusion Injury; STEMI
MeSH terms: Reperfusion Injury; ST Elevation Myocardial Infarction; Wounds and Injuries
Intervention: Bendavia (MTP-131); Placebo
Intervention description: 0.05 mg/kg/hr; Identically appearing placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Myocardial Reperfusion; Primary PCI; Stenting for ST-segment Elevation Myocardial Infarction

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).
    

Eligibility criteria:

        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.