COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction, a Phase II, Multicenter, Randomized, Double Blinded, Placebo Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 194
- 试验地点
- 8
- 主要终点
- infarct size (in % of LV mass) as estimated by CMR
研究概览
简要总结
Inflammatory processes have been identified as key mediators of ischemia/ reperfusion injury in ST-segment elevation myocardial infarction. They add additional damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. All the different anti-inflammatory approaches to reduce reperfusion injury have been disappointing.
Colchicine is a well-known substance with potent anti-inflammatory properties. In a recent pilot study performed in 151 acute STEMI patients treated with primary percutaneous coronary intervention(PPCI) Deftereos et al. showed a 50% reduction of infarct size (creatine kinase release) with a short course treatment of colchicine in comparison to placebo.
One mechanism to explain this effect could be the reduction of adverse left ventricular (LV) remodelling. LV remodelling is part of the healing process of myocardium after MI. It is defined as the end diastolic volume (EDV) increase in the first months after MI. Adverse LV remodelling is increased by inflammation and ultimately leads to heart failure.
Our main hypothesis is that colchicine with its anti-inflammatory properties significantly reduces the initiation of adverse LV remodelling, together with a significant reduction of infarct size and microvascular obstruction in comparison to placebo in acute STEMI patients referred for PPCI.
After inclusion and randomisation, patients will receive the first part of their experimental treatment: colchicine or placebo before PCI, then, the second part after PCI and during 5 days. They will be followed up during their hospitalization and until one year. In order to evaluate LV remodelling, two cardiac magnetic resonance studies will be performed during their participation: one during their hospitalization and a second at 3 months. At 1 year, adverse events will be collected by phone.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients, aged over 18 and <80 years,
- •Presenting within 12 hours of chest pain onset,
- •With ST segment elevation ≥ 0.2 mV in two contiguous leads or new onset of left bundle branch block,
- •Referral for primary percutaneous coronary intervention (PPCI).
- •Preliminary oral informed consent followed by signed informed consent as soon as possible
- •With an initially occluded coronary artery (TIMI angiographic flow of the culprit coronary artery ≤1)
排除标准
- •Patients with any legal protection measure,
- •Patients without any health coverage,
- •Patients with loss of consciousness or confused
- •Patients with a history of prior myocardial infarction
- •Patients with cardiogenic shock as defined by a systolic blood pressure <90 mmHg, despite 30 minutes of fluid challenge or requiring intravenous vasoactive agents (dobutamine, noradrenaline, adrenaline)
- •Patient with severe liver or known renal dysfunction (known GFR≤30 ml/min)
- •Patient with known history of severe drug intolerance to colchicine
- •Female patients currently pregnant or women of childbearing age not using contraception (oral diagnosis)
- •Patients with any obvious contraindication to magnetic resonance imaging (claustrophobia, pace maker, defibrillator....)
- •Patients treated by macrolides or pristinamycin
- •Chronic treatment with COLCHICINE (Mediterranean familial fever mainly)
- •Patient with lactose intolerance
- •Patient with swallowing disorders
研究组 & 干预措施
Colchicine
The patients will receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. during 5 days.
干预措施: Colchicine group (experimental arm) (Drug)
Control arm
The patients will receive an oral bolus of placebo of 2 mg followed by 0.5 mg b.i.d. during 5 days.
干预措施: Placebo group (control arm) (Drug)
结局指标
主要结局
infarct size (in % of LV mass) as estimated by CMR
时间窗: 5 days
The primary endpoint will be the infarct size as estimated by CMR at 5 days follow-up between both groups
次要结局
- LV ejection fraction(At 5 days)
- Relative ventricular remodeling (%)(at 3 months)
- LVEDV(At 3 months)
- LVESV(at 3 months)
- Relative LV ejection fraction(5 days)
- Absolute adverse left ventricular remodeling (mL)(at 3 months)
- Infarct size in % of LV mass(At 3 months)
- number of treatment discontinuation(5 days)
- Microvascular obstruction (in % of LV mass)(At 5 days)
- Percent of thrombi in the LV(At 5 days)
- Incidence of major adverse cardiovascular events(At 12 months)
- Quality of life assessed by the EuroQol-5D (EQ5D) questionnaire(At 12 months)
- number of adverse events(up to 5 days)
- Dosage of inflammation biomarkers(up to 3 months)