Trial of ACE Inhibition in Infants With Single Ventricle (A Trial Conducted by the Pediatric Heart Network)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 230
- 试验地点
- 9
- 主要终点
- Weight-for-age Z-score at 14 Months of Age
研究概览
简要总结
This study will evaluate the efficacy and safety of administering an angiotensin converting enzyme inhibitor (ACE-I) (enalapril) to infants with a functional single ventricle. The study will also compare the effect of ACE-I therapy to placebo on somatic growth and compare the effect of ACE-I therapy to placebo on signs and symptoms of heart failure, neurodevelopmental and functional status, ventricular geometry, function, and atrioventricular (AV) valve regurgitation. In addition, the study will determine the relationship between genetic polymorphisms linked to ventricular hypertrophy (enlarged heart) and the response to ACE-I therapy and compare the incidence of adverse events in subjects treated with ACE-I with those in subjects treated with placebo.
详细描述
BACKGROUND:
Growth impairment is common in infants and children with congenital heart disease, most often in the presence of congestive heart failure and/or cyanosis. Growth failure is noted in many infants with a single ventricle who manifest both cyanosis and heart failure that commonly persist after palliative surgery. Whether this impairment is related to persistent or progressive abnormalities in cardiac structure and function is not known. ACE-Is are widely used in the treatment of infants with severe congestive heart failure to improve cardiac function and somatic growth. The ability of an ACE-I to improve somatic growth in infants with a single ventricle has not been previously studied.
This study has been approved by the Institutional Review Boards/Research Ethics Boards of all participating clinical centers:
Hospital for Sick Children, Toronto, Canada
Children's Hospital Boston, Boston, MA
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 45 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Less than or equal to 45 days of age
- •Age greater than 1 week if born at 35 weeks gestation
- •Single ventricle physiology
- •Stable systemic and pulmonary blood flow
- •Planned Glenn shunt surgery (or variant known as hemi-Fontan)
排除标准
- •Birth weight less than or equal to 2.5 kg if gestational age is greater than or equal to 38 weeks
- •Birth weight less than the 10th percentile for gestational age if gestational age is 35 to 37 weeks
- •Less than 35 weeks gestation
- •Anatomic diagnosis of pulmonary atresia with intact ventricular septum
- •Less than 3 days after palliative cardiac surgical procedure, if performed
- •Aortic oxygen saturation less than 65%
- •Current mechanical ventilatory support
- •Current intravenous inotropic support
- •Creatinine greater than 1.0 mg/dL
- •Absolute neutrophil count less than 1,000 cells/mL
- •Chromosomal or recognizable phenotypic syndrome of noncardiac congenital abnormalities associated with growth failure (e.g., Trisomy 21, Noonan's syndrome, Turner's syndrome)
- •Prior ACE inhibitor use for greater than 7 consecutive days
研究组 & 干预措施
Enalapril
Enalapril (angiotensin converting enzyme inhibitor)
干预措施: Enalapril (Drug)
Placebo
Placebo (Ora-Plus and Ora-Sweet)
干预措施: Placebo (Drug)
结局指标
主要结局
Weight-for-age Z-score at 14 Months of Age
时间窗: Measured at baseline, 2 weeks after starting study drug, just prior to the Glenn surgery, 7 days after restarting drug following the Glenn surgery, at 10 months of age, and at 14 months of age
Weight-for-age z-score at 14 months of age. In primary analysis outcome is defined as predicted mean of weight z-score at age 14 months based on longitudinal modeling(and adjusted for baseline values)
次要结局
- Height-for-age Z-score(Measured at baseline, 2 weeks after starting study drug, just prior to the Glenn surgery, 7 days after restarting drug following the Glenn surgery, at 10 months of age, and at 14 months of age)
- B-Type Natriuretic Peptide(Measured just prior to the Glenn surgery)
- MacArthur-Bates Inventory -Phrases Understood(at 14 months of age)
- MacArthur-Bates Inventory -Words Understood(at 14 months of age)
- Number of Participants With Ross Heart Failure Class I(Measured at 14 months of age)
- B-type Natriuretic Peptide Level(at the time of the 14 month visit)
- Head Circumference-for-age Z-score(Measured at baseline, 2 weeks after starting study drug, just prior to the Glenn surgery, 7 days after restarting drug following the Glenn surgery, at 10 months of age, and at 14 months of age)
- Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score(at 14 months of age)
- Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score(at 14 months of age)
- Neurodevelopmental Status (FSII)(at 14 months of age)
- MacArthur-Bates Inventory -Total Gestures(at 14 months of age)
- MacArthur-Bates Inventory -Words Produced(at 14 months of age)
- Ejection Fraction (%)(at 14 months of age)
- Ventricular Mass(At 14 months of age)
- Ventricular Mass Z-score(at 14 months of age)
- End-diastolic Volume(at 14 months of age)
- End Diastolic Volume Z-score(just before the Glenn surgery)
- Ventricular Mass to Volume Ratio(Measured at 14 months of age)
- End-diastolic Volume Z-score(at 14 months of age)
- Ventricular Filling Pressure(just before the Glenn surgery)
- Number of Participants With Moderate to Severe AV Valve Regurgitation(at age 14 months)