Bivalirudin Infusion for Ventricular Infarction Limitation
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 78
- 试验地点
- 4
- 主要终点
- CMR Assessment Of Infarct Size At Day 5
研究概览
简要总结
The purpose of this study is to evaluate whether the use of bivalirudin will reduce extent of the damage done to the heart muscle in participants who suffered a heart attack, compared to the comparator treatment (heparin).
详细描述
The study will assess the effect of bivalirudin administration during primary percutaneous coronary intervention (PPCI) and for 4 hours (h) afterwards, looking at contrast enhanced cardiac magnetic resonance imaging (CMR) assessed infarct size and on circulating markers of thrombosis and cell injury in participants treated with PPCI for a large myocardial infarction (MI).
The objective of this study is to determine whether bivalirudin, compared to heparin [unfractionated heparin (UFH)], for PPCI in large ST segment elevation myocardial infarction (STEMI) can:
Primary Objective • Reduce infarct size assessed by CMR 5 days (defined as 5 days ±72 h from randomisation) after PPCI
Secondary Objectives of this study are to determine the effects of bivalirudin compared with UFH treatment for PPCI in STEMI on:
- Other CMR derived parameters of myocardial recovery 5 days after PPCI (that is, left ventricular ejection fraction [LVEF], myocardial salvage index [MSI], and micro-vascular obstruction [MVO])
- LVEF by CMR at 90 days
- Modulate markers of thrombin activity and cell injury after reperfusion
- Coronary flow and micro-circulation at the end of PPCI
- Survival at 90 days
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
- Single (Outcomes Assessor)
盲法说明
The primary endpoint was evaluated by a core lab totally blinded to clinical information and the treatment groups.
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
- •Experienced ischemic symptoms of >20 min and <12 h and had a diagnosis of STEMI with ST segment elevation of ≥1 mm in ≥2 contiguous precordial leads, or presumably new left bundle branch block
- •Provided written informed consent or witnessed consent in countries and sites where such participant consenting is applicable, before initiation of any study-related procedures
- •Had TIMI 0 or 1 flow in the IRA on initial angiogram
- •Fulfilled angiographic criteria/score for a large infarction based on initial angiogram (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease score of ≥21)
- •Were candidates for PPCI
- •Administration of an initial dose of 150 to 325 mg orally (or 250 to 500 mg IV) and a loading dose of any approved P2Y12 inhibitor
排除标准
- •Contraindication or known hypersensitivity to bivalirudin or UFH
- •Refusal to receive blood transfusion/products
- •Participants requiring staged coronary artery bypass graft procedure within the first 90 days
- •Known international normalized ratio ≥2 or known prothrombin time >1.5 times upper limit of normal on the day of the index PPCI, or known history of bleeding diathesis
- •Therapy with vitamin K antagonists within 72 h of PPCI
- •Therapy with dabigatran, rivaroxaban, or other oral anti-Xa or antithrombin agents within 48 h of PPCI
- •History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass, aneurysm, arteriovenous malformation, or recent head injury (within the last 5 days)
- •Participants with previous history of Q-wave MI
- •Known glomerular filtration rate (GFR) <30 milliliter/min or dialysis dependent
- •Major surgery within the previous 30 days
- •Minor surgery/biopsy exclusions in the past 3 days
- •Upper gastrointestinal or genitourinary bleed 30 days prior to randomization
- •Stroke or transient ischemic attack 30 days prior to randomization
- •Administration of thrombolytics or glycoprotein IIb/IIIa inhibitor 72 h prior to PPCI
- •Administration of enoxaparin 8 h prior to PPCI
- •Administration of bivalirudin 12 h prior to PPCI
- •Administration of fondaparinux or other low molecular weight heparin 24 h prior to PPCI
- •Known contraindications to aspirin or P2Y12 inhibitors
- •Known allergy that cannot be pre-medicated to iodinated contrast
- •Known contraindication to CMR
- •Women of child bearing potential (see below)
- •Previous enrollment (participants are considered enrolled upon Randomization) in this study
- •Treatment with other investigational drugs or devices within the 30 days preceding enrollment or planned use of other investigational drugs or devices before the primary endpoint of this study had been reached
- •Participants with a body weight >150 kg
- •Child bearing potential was defined as:
- •A female participant was considered to have childbearing potential unless she met at least 1 of the following criteria:
- •Age ≥50 years and naturally amenorrheic for ≥1 year (amenorrhea following cancer therapy did not rule out childbearing potential)
- •Premature ovarian failure confirmed by a specialist gynecologist
- •Previous bilateral salpingo-oophorectomy or hysterectomy
- •XY genotype, Turner's syndrome, uterine agenesis
研究组 & 干预措施
PPCI with Bivalirudin
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
干预措施: PPCI (Procedure)
PPCI with Bivalirudin
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
干预措施: Bivalirudin (Drug)
PPCI with Heparin
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
干预措施: PPCI (Procedure)
PPCI with Heparin
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
干预措施: Heparin (Drug)
结局指标
主要结局
CMR Assessment Of Infarct Size At Day 5
时间窗: 5 days post PPCI
Size of cardiac infarct, expressed as grams, as assessed by CMR. The use of CMR has dramatically improved the ability for accurate infarct size estimations and is therefore currently considered the gold standard. The number of participants and their mean reported infarct size, as grams, at Day 5 are presented.
次要结局
- CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5(5 days post PPCI)
- CMR Assessment Of LVEF At Day 90(90 days post PPCI)
- TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI(1 day (end of PPCI))
- CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5(5 days post PPCI)
- CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5(5 days post PPCI)
- Percentage of Participants With In-Hospital Net Adverse Cardiac Events (NACE) At Day 5(5 days post PPCI or at discharge, whichever occurs first)
- Death At Day 90(90 days post PPCI)