Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery Following Fontan Surgery: a Randomized, Double-blind, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Days Alive and Out of the Hospital Within 30 Days of Surgery.
研究概览
简要总结
The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.
The investigators will propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. The investigators plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The investigators hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery.
详细描述
The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Following this operation, deoxygenated blood flows passively from the body through the lungs without a pumping chamber. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.
We propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. We plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The primary aim of the study is to determine whether nesiritide, milrinone or placebo infusion is associated with fewer days alive and out of the hospital within 30 days of surgery. We hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery. Secondary aims are to determine the effects of these infusions on postoperative resource consumption, hemodynamics, arrhythmias, renal function, neurohumoral activation and adverse events. Thirty-nine patients per group (117 total patients) will be enrolled over three years.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing an elective, primary Fontan operation at Children's Hospital Boston.
排除标准
- •Revision surgery for failing Fontan circulation.
- •Preoperative serum creatinine > 1.5 mg/dL or chronic dialysis.
- •The attending surgeon, cardiac anesthesiologist, or cardiac intensivist has a compelling indication to initiate either nesiritide or milrinone outside of the confines of the study.
研究组 & 干预措施
I- nesiritide
Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.
干预措施: nesiritide (Drug)
II- Milrinone
Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.
干预措施: milrinone (Drug)
III- placebo
Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met.
干预措施: placebo (Drug)
结局指标
主要结局
Days Alive and Out of the Hospital Within 30 Days of Surgery.
时间窗: 30 days
次要结局
- Cardiovascular: Cardiac Index(Postoperative hour #8)
- Cardiovascular: Peak Lactate Level(Initial 24 hours in CICU)
- Cardiovascular: Arrhythmia(Postoperative day (POD) #0 through 5)
- Renal Function: Urine Output(first 24 hours CICU admit)
- Cardiovascular: Peak Inotrope Score(Initial 24 hours in CICU)
- Renal Function: Maximum Change in Serum Creatinine(14 days after surgery)
- Resource Utilization: Hours of Mechanical Ventilation Until Initial Extubation(From Fontan operation until initial extubation, assessed during initial CICU stay, up to 30 days.)
- Resource Utilization: Days of Initial CICU Stay(From Fontan operation until initial discharge from the CICU, assessed during the postoperative hospitalization, up to 90 days.)
- Resource Utilization: Chest Tube Days(From Fontan operation until final chest tube removed, assessed during postoperative hospitalization, up to 90 days.)
- Resource Utilization: Days Alive and Out of Hospital Within 180 Days of Surgery(180 days)
- Plasma Norepinephrine Levels.(Preoperative baseline to 24 hours after CICU admission)
- Epinephrine Levels(Preoperative baseline to 24 hours after CICU admission)
- N-terminal Pro-brain Natriuretic Peptide Levels(Preoperative baseline to 24 hours after CICU admission)
研究者
John M Costello
Associate in Cardiology
Boston Children's Hospital