A Phase III Double-Blind, Randomized, Placebo Controlled, Multi-Center Clinical Study to Evaluate the Efficacy and Safety of Intravenous L-citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Subjects Undergoing Surgery for Congenital Heart Defects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 189
- 试验地点
- 29
- 主要终点
- A Composite Variable Consisting of the Longer of Either (1) Length of Time on Mechanical Ventilation or (2) Length of Inotrope Use.
研究概览
简要总结
The purpose of this study is to determine whether L-citrulline is effective and safe in the prevention of clinical sequelae of Acute Lung Injury in pediatric subjects undergoing surgery for congenital heart defects.
详细描述
This is a randomized, double-blind, placebo controlled, multicenter study that will compare the efficacy and safety of L-citrulline versus placebo in subjects undergoing surgery for congenital heart defects.
Eligible subjects undergoing repair of a large unrestrictive ventricular septal defect (VSD), a partial or complete atrioventricular septal defect (AVSD), or an ostium primum atrial septal defect (primum ASD) will be eligible for enrollment in this study.
Each enrolled subject will be randomized to receive either L-citrulline or placebo throughout all administrations in the study. Subjects will receive an L-citrulline bolus of 150 mg/kg or placebo at the initiation of cardiopulmonary bypass, the addition of L-citrulline at a concentration of 200 μmol/L or placebo given as a bolus during bypass. This may be administered as a one-time bolus or multiple administrations to compensate for fluids containing L-citrulline that may be removed from the patient during the course of the operation and thus to maintain the concentration of 200 μmol/L. L-citrulline bolus of 20 mg/kg or placebo 30 minutes after decannulation from cardiopulmonary bypass, followed immediately by a 9 mg/kg/hr continuous L-citrulline infusion or placebo for up to 48 hours.
The study drug or placebo infusion will be discontinued once invasive arterial blood pressure monitoring is discontinued or at 48 hours, whichever comes first. Subjects will be followed until Day 28 or discharge from the hospital, whichever comes first. For subjects discharged prior to Day 28, a final assessment via telephone will be conducted at Day 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects, parents, or legal guardian of the subject who are willing and able to sign informed consent
- •Male and female subjects aged ≤18 years of age
- •Infants, children and adolescents undergoing cardiopulmonary bypass (CPB) for repair of a large unrestrictive VSD, an ostium primum ASD, or a partial or complete AVSD
- •Pre-operative echocardiogram which confirms the cardiovascular anatomy and defect to be surgically repaired
排除标准
- •Evidence of pulmonary artery or vein abnormalities on the pre-operative echocardiogram that will not be addressed surgically. Specific abnormalities excluded include the following:
- •Significant pulmonary artery narrowing not amenable to surgical correction
- •Previous pulmonary artery stent placement
- •Significant left sided AV valve regurgitation not amenable to surgical correction
- •Pulmonary venous return abnormalities not amenable to surgical correction
- •Pulmonary vein stenosis not amenable to surgical correction
- •Preoperative requirement for mechanical ventilation or intravenous inotrope support
- •Presence of fixed or idiopathic pulmonary hypertension (i.e. Eisenmenger's Syndrome) prior to surgical repair
- •Pre-operative use of medications to treat pulmonary hypertension
- •Pregnancy; Females of child-bearing potential must be willing to participate an acceptable method of birth control for the duration of study participation (e.g. oral contraceptive, hormonal implant, intra-uterine device)
- •Any condition which, in the opinion of the investigator, might interfere with the study objectives
- •Participation in another clinical trial within 30 days of Screening or while participating in the current study, including the 28 days of follow-up post study drug administration
研究组 & 干预措施
L-citrulline
- Bolus of 150 mg/kg at the initiation of cardiopulmonary bypass, but after removal of any crystalloid base;
- Addition of study medication at a concentration of 200 μmol/L given as a bolus during bypass. This may be administered as a one-time bolus or multiple administrations to compensate for fluids containing L-citrulline that may be removed from the patient during the course of the operation and thus to maintain the concentration of 200 μmol/L;
- Bolus of 20 mg/kg 30 minutes after decannulation from cardiopulmonary bypass;
- 9 mg/kg/hr continuous infusion for up to 48 hours.
干预措施: L-citrulline (Drug)
Placebo
- Bolus of 150 mg/kg at the initiation of cardiopulmonary bypass;
- Addition of placebo matched for volume given as a bolus during bypass. This may be administered as a one-time bolus or multiple administrations during bypass;
- Bolus of 20 mg/kg 30 minutes after decannulation from cardiopulmonary bypass;
- 9 mg/kg/hr continuous infusion for up to 48 hours.
干预措施: Placebo (Other)
结局指标
主要结局
A Composite Variable Consisting of the Longer of Either (1) Length of Time on Mechanical Ventilation or (2) Length of Inotrope Use.
时间窗: 28 Days
Mechanical ventilation (MV) = invasive or noninvasive MV incl. bilevel (biphasic) positive airway pressure or continuous positive airway pressure. Inotrope use = medications considered within the derivation of total inotrope score (dopamine, dobutamine, milrinone, epinephrine, phenylephrine, norepinephrine). Both measures recorded until earliest of subject hospital discharge or Day 28.
次要结局
- Length of Time on Positive Pressure Ventilation(28 Days)
- Thoracotomy Output(28 Days)
- Length of Time on Vasodilators(28 Days)
- Length of Hospitalization(28 Days)
- Hemodynamic Improvement: Central Venous Pressure(2 Days)
- Length of Time of Inotrope Use(28 days)
- Inotrope Score(Up to 48 hours after separation from CBP)
- Hemodynamic Improvement: Systemic Arterial Blood Pressure(2 Days)
- Hemodynamic Improvement: Oxygen Saturation(2 Days)
- Length of Time of Intubation(28 Days)
- Length of Pediatric Intensive Care Unit (PICU) Stay(28 Days)
- Occurrence of Adverse and Serious Adverse Events(28 Days)
- Length of Time on Mechanical Ventilation(28 Days)
- Hemodynamic Improvement: Heart Rate(2 Days)
- Number of Patients With Refractory Hypotension(2 Days)
- Patients With Plasma Concentrations of Citrulline(28 Days)