Exenatide for Myocardial Protection During Reperfusion Study: A Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 198
- 试验地点
- 10
- 主要终点
- Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI)
研究概览
简要总结
This study aims to assess the effect of exenatide on myocardial injury in patients undergoing emergent percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction or heart attack (STEMI).
详细描述
This is a Phase II randomized, double-blind, placebo-controlled study of patients with STEMI. Those who agree to participate will be immediately randomized to one of two groups: a 24-h infusion of exenatide; or a 24 h infusion of placebo. We will assess the ability of exenatide to reduce ischemic injury. This study will serve as safety evaluation study as well as a pilot for a larger multicentre trial powered for clinical outcomes.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admission for primary PCI for STEMI, with enrollment within 12 hours of onset of symptoms. STEMI will be defined as typical ECG changes (ST segment elevation ≥1mm in 2 or more limb leads, or ≥2mm in 2 or more precordial leads, or new onset LBBB) associated with acute chest pain or an elevation of cardiac enzymes.
- •Antegrade TIMI 0 or 1 prior to PCI in the infarct-related artery
- •Age ≥18 years
排除标准
- •Symptomatic hypoglycemia (serum glucose <3.3 µmol/L; 60 mg/dl)
- •Diabetes mellitus requiring insulin therapy
- •Diabetic ketoacidosis
- •Coronary anatomy warranting emergent coronary artery bypass graft surgery
- •Mechanical complication of STEMI (ventricular septal rupture, free wall rupture, acute severe mitral regurgitation)
- •Need for hemodialysis
- •Malignancy, HIV, or central nervous system disorder
- •Cardiopulmonary resuscitation >15 min and compromised level of consciousness.
- •Cardiogenic shock
- •Current participation in any research study involving investigational drugs or devices
- •Inability to give informed consent
- •Inability to safely undergo cMRI (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, implanted drug infusion device, bone growth/fusion stimulator, cochlear, otologic, or ear implant, severe claustrophobia)
- •Women of childbearing potential who are known to be pregnant or lactating or who have a positive pregnancy test on admission
- •History of pancreatitis
- •Known end stage renal failure or known eGFR <30 mL/min
- •Currently taking exenatide (Byetta, Bydureon), liraglutide (Victoza), or any other GLP-1 agonist
研究组 & 干预措施
Exenatide
o Exenatide at a dose of 1.5 µg IV over 30 min followed by 1.2 µg/hr IV for 1.5 h (Rate1), followed by 1.9 µg/hr IV* for 22 h (Rate 2)
*Once the creatinine clearance is available, if the value is <60 mL/min, the rate at 2 hours will be maintained at Rate 1 for the duration of the infusion. If the value becomes available after the 2-hour point, and the rate has already been changed to Rate 2, the infusion will be titrated back down to Rate 1 if the creatinine clearance is <60 mL/min.
If the creatinine clearance is <30 mL/min, the infusion will be discontinued and the patient will otherwise continue with all study procedures.
A bolus administration of study medication is initiated preferably prior to reperfusion, or, if not possible, up to 30 minutes after the start of reperfusion to avoid delays in door-to-door balloon times.
干预措施: Exenatide (Drug)
Placebo
o Placebo bolus over 30 min followed by placebo infusion at 'Rate 1' for 1.5 h, followed by 'Rate 2' for 22 hours*.
干预措施: Placebo (Drug)
结局指标
主要结局
Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI)
时间窗: 3 months
次要结局
- Blood glucose < 3.0 mmol/L(During index hospitalization (up to 6 months))
- Hypotension (defined as SBP <90 mmHg)(During index hospitalization (up to 6 months))
- Left ventricular volume(3 months)
- Unplanned repeat revascularization(6 months)
- Development of heart failure(6 months)
- Cardiogenic shock(During index hospitalization (up to 6 months))
- Infarct size/area of risk (measured by cMRI)(3 months)
- Left ventricular global and regional LV systolic ejection fraction(3 months)
- Myocardial enzyme levels (troponin I and CK-MB)(24 hours)
- Angiographic myocardial blush score(At the time of the PCI procedure)
- Serum glucose concentration(72 hours)
- Inflammatory marker levels (interleukin-6, interleukin-10, TNF-alpha)(24 hours)
- NT-proBNP blood levels(24 hours)
- Death(6 months)
- ST segment elevation resolution (measured by ECG)(3 months)
- Myocardial infarction (heart attack)(3 months)
- Measure of extent of heart failure (NYHA classification)(3 months)
- Major adverse cardiac events (defined as a combined outcome of death, recurrent myocardial infarction, stroke, and unplanned repeat revascularization)(6 months)
- Recurrent myocardial infarction (heart attack)(6 months)
- Stroke(6 months)
研究者
Vladimír Džavík
Director, Research and Innovation in Interventional Cardiology and Cardiac Intensive Care, Division of Cardiology
University Health Network, Toronto