Randomized Embedded Multifactorial Adaptive Platform in ExtraCorporeal Membrane Oxygenation - Beta Receptor Modulation Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change (delta) in heart rate 24 hours after randomization.
研究概览
简要总结
In this phase 2, single center, randomized clinical pilot trial, investigators will study the effect of a strategy involving a reduction of beta receptor (BR) stimulation (by decreasing dobutamine dosages) and subsequent BR inhibition (through ultra-short acting betablockers), versus a (routine) strategy with continued BR stimulation through dobutamine infusion, on heart rate in patients with cardiogenic shock due to left- or bi-ventricular failure being supported by V-A ECMO.
详细描述
Despite the great benefits of Venoarterial ExtraCorporeal Membrane Oxygenation (V-A ECMO) and its rapidly increasing usage, even today, 30 till 70 percent of patients cannot be weaned from ECMO support and up to 50 percent of patients will eventually die in the first year. These high incidences of mortality and failure to wean from V-A ECMO support seem largely attributable to failure of the heart to recover in the context of inotropic drug administration and high sympathetic drive due to severe illness (further stressing an already failing heart). As V-A ECMO support creates a "safety window" where organ perfusion no longer relies on native cardiac output, therapeutic focus could be shifted to cardioprotective treatments. Cardioprotective treatments typically include beta blockers (BB) which have unequivocally shown benefits on mortality and morbidity in other patient categories with heart failure with reduced ejection fraction (HFrEF).
The investigators hypothesize that, in selected patients with cardiogenic shock undergoing V-A ECMO support, application of BBs is feasible and safe, and can effectively reduce heart rate.
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
- None
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
- •Age ≥ 18 years,
- •Having received V-A ECMO support for severe circulatory insufficiency due to left- or bi-ventricular failure.
- •≤ 16 hours after initiation of V-A ECMO support
- •Receiving ≥ 2 mcg/kg/min of dobutamine.
- •Norepinephrine infusion ≤ 0.4 mcg/kg/min
- •Heart rate ≥ 80 bpm (being sinus rhythm, atrial fibrillation or atrial flutter) after V-A ECMO initiation
排除标准
- •Objection during the deferred consent procedure
- •V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention).
- •Concomitant durable Left Ventricular Assist Device (LVAD)
- •Polymorphic ventricular tachycardia necessitating BB therapy
- •Isolated right ventricular failure (e.g. due to pulmonary embolism)
- •Need of high dose dobutamine > 6.0 mcg/kg/min
- •Epinephrine infusion
- •Signs of insufficient trans cardiac flow:
- •Absence of aortic valve opening
- •Pulse pressure <10 mmHg (with intra-aortic balloon pump (IABP) standby)
- •Spontaneous contrast in the heart at echocardiography
- •Contraindications for-, intolerance to- or allergy to esmolol
- •Second- or third- degree AV block
- •Pregnancy
- •Life expectancy of less than 24 hours
- •Participation in another randomized clinical trial (e.g. On Scene trial or Left Ventricular unloading trial)
- •Inability to start study treatment within 4 hours after randomization
- •Post heart transplantation patients
研究组 & 干预措施
Beta receptor inhibition arm
In the "beta receptor (BR) inhibition arm", patients are randomized to a biphasic strategy where BR stimulation is phased out and esmolol (BR blockade) is initiated in a sequential way. During a first phase, milrinone (a phosphodiesterase inhibitor which is routinely used in V-A ECMO supported patients) infusion will be initiated (if not already being given) at 0.25 mcg/kg/min and dobutamine dosages will be decreased every hour and eventually stopped according to the following sequence; 6 - 4 - 2 - 1 - 0 mcg/kg/min.
In a second phase, esmolol is initiated with a dosage of 25 mcg/kg/min. The dose of the BB will be increased with increments of 25 mcg/kg/min every hour until reaching a heart rate between 50 and 70 bpm or a maximum dose of 200 mcg/kg/min. Prior to each dosage escalation, a reassessment of the hemodynamic situation will be done.
The BR inhibition strategy will be continued until 48 hours after randomization or earlier when deemed necessary by the treating physician.
干预措施: Esmolol (Drug)
结局指标
主要结局
Change (delta) in heart rate 24 hours after randomization.
时间窗: 24 hours after randomization
The average heart rate on basis of all observations during 5 minutes at both time points (t=0 and t=24h).
次要结局
- Myocardial oxygen consumption(At 24 and 48 hours after randomization)
- Vasopressor score(at baseline, 24 and 48 hours)
- Stroke volume index(at baseline, 24 and 48 hours)
- Maximum median dosages of esmolol(after 48 hours)
- Tricuspid annular plane systolic excursion (TAPSE).(at baseline, 24 and 48 hours)
- Positive End Expiratory Pressure (PEEP) level(At 24 and 48 hours after randomization)
- Left ventricular outflow tract velocity time integral (LVOT VTI)(at baseline, 24 and 48 hours)
- Lactate level(at baseline, 24 and 48 hours)
- Plasma NT-proBNP levels(At baseline and 48 hours after randomization)
- Plasma Creatine Kinase MB levels(At baseline and 48 hours after randomization)
- Plasma metanephrine levels(At baseline and 24 after randomization)
- Plasma normetanephrines levels(At baseline and 24 after randomization)
- Percentage of patients having received esmolol(after 48 hours)
- Occurrence of new onset ventricular and/or atrial arrhythmias after randomization(during the first 48 hours)
- Cardiac output(at baseline, 24 and 48 hours)
- Pulmonary capillary wedge pressure(at baseline, 24 and 48 hours)
- Troponin(At 24 and 48 hours after randomization)
- Central venous pressure(at baseline, 24 and 48 hours)
- Mixed venous oxygen saturation (SvO2)(at baseline, 24 and 48 hours)
- FiO2 suppletion(At 24 and 48 hours after randomization)
- Ejection fraction (EF)(at baseline, 24 and 48 hours)
研究者
Christiaan Meuwese
Cardiologist-Intensivist
Erasmus Medical Center