Effect of Early Use of Levosimendan Versus Placebo on Top of a Conventional Strategy of Inotrope Use on a Combined Morbidity-mortality Endpoint in Patients With Cardiogenic Shock
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 610
- 试验地点
- 28
- 主要终点
- Proportion of All-cause mortality
研究概览
简要总结
Cardiogenic shock (CS) mortality remains high (40%). Despite their frequent use, few clinical outcome data are available to guide the initial selection of vasoactive drug therapies in patients with CS. Based on experts' opinions, the combination of norepinephrine-dobutamine is generally recommended as a first line strategy. Inotropic agents increase myocardial contractility, thereby increasing cardiac output. Dobutamine is commonly recommended to be the inotropic agent of choice and levosimendan is generally used following dobutamine failure. It may represent an ideal agent in cardiogenic shock, since it improves myocardial contractility without increasing cAMP or calcium concentration. At present, there are no convincing data to support a specific inotropic agent in patients with cardiogenic shock. Our hypothesis is that the early use of levosimendan, by enabling the discontinuation of dobutamine, would accelerate the resolution of signs of low cardiac output and facilitate myocardial recovery.
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)
盲法说明
The study will be double-blinded. Investigator masking to group assignment after randomization will be guaranteed by use of a placebo.
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
- •Adult patient ≥ 18 years with cardiogenic shock defined by:
- •Adequate intravascular volume
- •Norepinephrine to maintain MAP at least at 65 mmHg for at least 3 hours and less than 24h. At inclusion the dose must be <1 microgram/kg/min under norepinephrine base or <2 microgram/kg/min under norepinephrine tartrate, OR/AND Dobutamine since at least 3h and less than 24h at inclusion.
- •Tissue hypoperfusion: at least 1 sign within 24h prior to inclusion (lactate ≥ 2 mmol/l; mottling, capillary refeel time > 3 seconds, oliguria <500ml/24h or ≤ 20 ml/h during the last 2 hours, ScVO2 ≤ 60% or veno-arterial PCO2 gap ≥ 5 mmHg);
排除标准
- •Myocardial sideration after cardiac arrest of non-cardiac etiology
- •Immediate or anticipated (within 6 hours) indication of Extra Corporel Life Support
- •Use of VA-ECMO or IMPELLA or LVAD;
- •Chronic renal failure requiring hemodialysis
- •Cardiotoxic poisoning
- •Septic cardiomyopathy
- •Previous levosimendan administration within 15 days
- •Cardiac arrest with non-shockable rhythm;
- •No flow time higher > 3 minutes;
- •Cardiac arrest with unknown no flow duration;
- •Total duration of cardiac arrest (no flow plus low flow) > 45 minutes;
- •Cerebral deficit with fixed dilated pupils
- •Patient moribund on the day of enrollment
- •Irreversible neurological pathology
- •Known hypersensitivity to levosimendan or placebo, or one of its excipients
- •Pregnant woman, birthing or breastfeeding mother
- •Minor (not emancipated)
- •Person deprived of liberty for judicial or administrative decision;
- •Adult subject to a legal protection measure (such as guardianship, conservatorship)
研究组 & 干预措施
Levosimendan
Experimental group: patients with cardiogenic shock treated with levosimendan in addition to the conventional strategy.
干预措施: Levosimendan 2.5 MG/ML Injectable Solution (Drug)
Placebo
Control group: Patients with cardiogenic shock treated with placebo (Cernevit/Soluvit) in addition to the conventional strategy.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of All-cause mortality
时间窗: Day 30 following randomization
Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)
Proportion of Extra Corporel Life Support implantation
时间窗: Day 30 following randomization
Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)
Proportion of Dialysis
时间窗: Day 30 following randomization
Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)
次要结局
- Proportion of death.(Day 90)
- Proportion of urgent coronary revascularization(Day 90)
- number of cardiovascular events(Day 90)
- Time to death(Day 90)
- Time to escalation to permanent left ventricular assist device or cardiac transplantation(Day 90)
- Time to dialysis(Day 90)
- Time to ECLS requirement(Day 90)
- Proportion of All-cause mortality(days 7, 60, and 180 days and 12 months)
- Proportion of Dialysis(Day 90)
- Number of dobutamine free days(From randomization to day 30)
- Number of vasopressors free days(From randomization to day 30)
- Number of ventilatory free days(From randomization to day 30)
- proportion of re-hospitalization for heart failure(days 180 and at 12 months)
- Proportion of Extra Corporel Life Support implantation(days 180 and at 12 months)
- Proportion of dialysis(days 180 and at 12 months)
- Proportion of cardiac transplantation(Day 90)
- Proportion of escalation to permanent Left Ventricular Assist Device(Day 90)
- Proportion of stroke(days 180 and at 12 months)
- Proportion of recurrent myocardial infarction(days 180 and at 12 months)
- Proportion of re-hospitalization for heart failure(Day 90)
- Number of renal replacement free days(D 30, 60, 180 and at 12 months)
- Lactate clearance(from randomization to day 7)
- Duration of intensive care unit stay(Up to Intensive Care Unit discharge (assessed up to 1 month))
- Duration of hospitalization(Up to hospitalization discharge (assessed up to 1 month))
- Proportion of death(days 180 and at 12 months)
- proportion of cardiac transplantation(days 180 and at 12 months)
- proportion of escalation to permanent left ventricular assist device(days 180 and at 12 months)
- Proportion urgent coronary revascularization(days 180 and at 12 months)
- Occurrence of arrhythmias requiring therapy(from randomization to intensive care unit discharge.)
- the changes in biomarkers(from randomization to intensive care unit discharge.)
- All-cause mortality and/or ECLS and/or dialysis(At intensive care unit discharge)
研究者
Pr Bruno LEVY
Investigator coordonnator
Central Hospital, Nancy, France