Inhaled Milrinone and Epoprostenol for the Prevention of Difficult Cardiac Pulmonary Bypass Separation: A Randomized, Double-blind, Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 141
- 试验地点
- 1
- 主要终点
- Proportion of patients who have a difficult CPB weaning in both groups
研究概览
简要总结
In cardiac surgery, the presence of pulmonary hypertension (PH) is a prognostic factor associated with increased mortality and morbidity. In this context, one of the main causes of PH is related to reperfusion ischemia during weaning from extracorporeal circulation (CPB). One of the consequences of PH is right ventricular dysfunction. During weaning from CPB, the development of a right ventricular dysfunction is associated with increased requirements for vasopressor and inotropic agents, duration of mechanical ventilation, prolonged intensive care and hospital stay, and increased mortality compared with patients with left ventricular (LV) dysfunction. The management of patients with PH with or without right ventricular (RV) dysfunction relies on several strategies such as the administration of intravenous and inhaled agents, or mechanical ventricular support. Among those agents, the administration of inotropes or pulmonary vasodilators such as epoprostenol, milrinone and nitric oxide are among the most widely used treatments recommended by the Canadian Cardiovascular Society. At the Montreal Heart Institute, inhaled epoprostenol and milrinone are routinely administered to patients with PH or LV dysfunction in the perioperative setting. Despite the frequent use of inhaled epoprostenol and milrinone, Health Canada has not yet approved the use of these molecules.
The primary objective of this multicenter, double-blind, randomized clinical trial is to evaluate the clinical efficacy of the combined administration of inhaled epoprostenol and milrinone in a cardiac surgery setting. This trial will compare the clinical outcome of 71 patients who will receive inhaled epoprostenol and milrinone before the start of bypass surgery to 71 patients who will receive a placebo before the start of the CPB. The primary clinical outcome is the proportion of patients with an "unsuccessful" CPB weaning defined by the use of an inotrope +/- vasopressor agent or the use of mechanical circulatory support or a return to bypass grafting for hemodynamic reasons.
This clinical trial will evaluate the clinical efficacy of the combination of inhaled agents in a cardiac surgery setting. Therefore, if the results of this study are positive, the combination of inhaled epoprostenol and milrinone will optimize the management of patients with pulmonary hypertension with or without a right ventricular dysfunction.
详细描述
Hypothesis: Based on the knowledge gained from previous work, the administration of inhaled Milrinone and Epoprostenol therapy prior to the initiation of cardiopulmonary bypass (CPB) is superior in terms of favourable clinical outcomes. The combined administration of these agents improves right ventricular performance while reducing myocardial and pulmonary ischemia-reperfusion injury secondary to weaning from bypass surgery. For these reasons, we hypothesize that administration of combination therapy before the start of CPB may provide better hemodynamic stability throughout the surgery and favourable postoperative clinical outcomes.
Objective:
Primary Objective To determine whether the use of inhaled Epoprostenol and Milrinone, prior to the initiation of CPB, decreases the occurrence of difficult CPB weaning compared to placebo administration.
Secondary Objectives To determine the effect of combined use of inhaled Epoprostenol and Milrinone, prior to the initiation of CPB on hemodynamic and perioperative parameters.
To determine the effect of combined use of inhaled Epoprostenol and milrinone, prior to the initiation of CPB on postoperative 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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- Only patients undergoing cardiac surgery with CPB and aged 18 years and older will be included in this study.
排除标准
- •The presence of congenital cardiomyopathy, which the correction is the primary objective of the proposed surgery. For example, a patient who requires surgery for atrial septal defect closure only would not be eligible for the study. On the other hand, a patient who undergoes this same surgery in addition to a valve replacement, for example, would be eligible to participate in the study.
- •Heart transplant or ventricular assist device surgery
- •Urgent surgery including hemodynamic instability requiring vasopressor agents upon arrival in the operating room
- •A contraindication to transesophageal ultrasound monitoring or the presence of an unstable cervical spine.
- •Presence of a contraindication related to Epoprostenol or Milrinone administration such as a documented left ventricular or right ventricular outflow tract obstruction, a severe unaddressed aortic stenosis, or a documented allergy to either of these two molecules.
研究组 & 干预措施
Normal Saline
The control group will receive a saline solution (8mL) as a placebo, before CPB start.
干预措施: Normal saline (Drug)
Combination of inhaled Epoprostenol and Milrinone
The experimental group will receive simultaneously 4mg of Milrinone (1mg/mL, 4mL) and 60 mcg of Epoprostenol (15 mcg/mL, 4mL) before CPB initiation.
干预措施: Combined Epoprostenol Sodium & Milrinone (Drug)
结局指标
主要结局
Proportion of patients who have a difficult CPB weaning in both groups
时间窗: 1 year
To determine whether the use of inhaled Epoprostenol and Milrinone, prior to the initiation of CPB, decreases the occurrence of difficult CPB weaning compared to placebo administration.
次要结局
- Correlation between the variation of central venous pressure and patients who received the treatment(1 year)
- Correlation between fluid administration during surgery and patients who received the treatment(1 year)
- Correlation between the post-operative complications and patients who received the treatment(1 year)
- Correlation between the PAM/ PAPM ratio taken at T0 and T1 and patients who received the treatment(1 year)
- Correlation between right ventricular contractility and patients who received the treatment(1 year)
- Correlation between the vasoactive and inotropic score and patients who received the treatment(1 year)
- Correlation between right ventricular outflow tract obstruction and patients who received the treatment(1 year)
- Correlation between the variation of cardiac output and patients who received the treatment(1 year)
- Correlation between the right ventricular curve etiology (normal, square root, oblique) and patients who received the treatment(1 year)
- Correlation between the cardiac index taken at T0 and T1 and patients who received the treatment(1 year)
- Correlation between cerebral saturation and patients who received the treatment(1 year)
- Correlation between the time of persistent organ dysfunction (TPOD) and patients who received the treatment(1 year)
- Correlation between the ICU stay and patients who received the treatment(1 year)
- Correlation between the variation of arterial pressure and patients who received the treatment(1 year)