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 and Stenting for ST-segment Elevation Myocardial Infarction Infarction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 30
- 主要终点
- Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
Bendavia™
Bendavia™ administered intravenously at 0.05 mg/kg/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.
干预措施: Bendavia (MTP-131) (Drug)
Placebo
Placebo administered intravenously at 60 mL/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.
干预措施: Placebo (Drug)
结局指标
主要结局
Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
时间窗: 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
次要结局
- AUC of Troponin 1 Enzyme(Initial 24 and 72 hours post-PCI)
- Thrombosis in Myocardial Infarction (TIMI) Perfusion Grade Flow at Completion of PCI(Initiation to Completion of PCI, no longer than 4 hours)
- Change in Serum Creatinine From Baseline(Day 30 +7)
- Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline(Day 30 +/- 7)
- Blood Urea Nitrogen (BUN) Change From Baseline(Baseline to Day 30)
- Immediate Myocardial Complications: Mechanical Complications(Baseline up to 1 hour post-PCI)
- Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass(Day 30 + 7)
- Corrected TIMI Frame Count(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(pre-PCI to 24 hours post-PCI)
- Cystatin C Change From Baseline(Day 30 + 7)
- Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation(Baseline up to 1 hour post-PCI)
- Emergency Use of Medications During PCI Procedure(Initiation to Completion of PCI, no longer than 4 hours)
- Number and Percent of Grade 1 Episode of Contrast-Induced Nephropathy Post-PCI(Baseline to 48 hours post PCI or MRI)
- High Sensitivity C-Reactive Protein (hsCRP): Change From Baseline to Day 30(Baseline to Day 30)
- ProB-type Natriuretic Peptide (NT-proBNP) Change From Baseline to Day 30(Baseline to Day 30)
- Left Ventricular (LV) Ejection Fraction (%)(Day 4 to Day 30)
- Difference Between Left Ventricular End Diastolic Volume, Corrected(Day 4 and Day 30)
- Difference Between Left Ventricular End Systolic Volume, Corrected(Day 4 and Day 30)
- Chronic Heart Failure(Within 24 hours after PCI)