A Multi-center Randomized Trial of Laparotomy vs. Drainage as the Initial Surgical Therapy for ELBW Infants With Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP): Outcomes at 18-22 Months Adjusted Age
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 529
- 试验地点
- 44
- 主要终点
- Death or Neurodevelopmental Impairment (NDI)
研究概览
简要总结
This study will compare the effectiveness of two surgical procedures -laparotomy versus drainage - commonly used to treat necrotizing enterocolitis (NEC) or isolated intestinal perforations (IP) in extremely low birth weight infants (≤1,000 g). Infants diagnosed with NEC or IP requiring surgical intervention, will be recruited. Subjects will be randomized to receive either a laparotomy or peritoneal drainage. Primary outcome is impairment-free survival at 18-22 months corrected age.
详细描述
Necrotizing enterocolitis (NEC) is a condition, generally affecting premature infants, in which the intestines become ischemic (lack oxygen and/or blood flow). NEC occurs in up to 5-15% of extremely low birth weight (ELBW) infants. Isolated or focal intestinal perforation (IP) is a less common condition, affecting an estimated 4% of ELBWs, in which a hole develops in the intestines leaking fluid into the abdominal cavity. Outcome for infants with NEC and/or IP is poor: 49% die and half of the surviving infants are neurodevelopmentally impaired.
Surgical options for NEC and IP include two possible procedures: peritoneal drainage, in which a tube is placed in the abdominal cavity through a small incision for fluid to drain out; or laparotomy, in which an incision is made in the abdomen and necrotic intestine is removed. Drainage may be followed by a laparotomy.
The Neonatal Research Network's observational study of 156 ELBW infants with NEC or IP (Pediatrics. 2006 Apr; 117(4): e680-7) showed comparable outcomes for the two procedures before hospital discharge, but suggested an advantage of laparotomy over drainage at 18-22 months corrected age with lower rates of death or neurodevelopmental impairment. However, the infants that underwent laparotomy were more mature; infants with drains were smaller and more premature. We hypothesize that initial laparotomy may improve an infant's long-term neurodevelopmental outcome, potentially by reducing the maximum severity or duration of inflammation.
This study included a randomized controlled trial to compare the effectiveness of laparotomy versus drainage for treating NEC or IP in extremely low birth weight infants. Target enrollment is 300 infants diagnosed with NEC or IP for randomization to receive initially either a laparotomy or drainage. Subsequent laparotomies may be performed on infants in either group, if their condition continues to deteriorate. Surviving infants will return for a follow-up assessment at 18-22 months corrected age.
This study also attempted to use a comprehensive cohort design that would have added additional information beyond the conventional randomized trial component. The cohort component included trial data among eligible, non-randomized infants with NEC/IP, who consented for the non-randomized cohort, would be collected and analyzed as a secondary specific aim. This additional cohort was called the preference cohort.
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
- — 至 8 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants born at ≤1,000 g birth weight
- •Infant is ≤8 0/7 weeks of age at the time of eligibility assessment
- •Pediatric surgeon decision to perform surgery for suspected NEC or IP
- •Subject is at a center able to perform both laparotomy and drainage
排除标准
- •Major anomaly that influences likelihood of developing primary outcome or affects surgical treatment considerations
- •Congenital infection
- •Prior laparotomy or peritoneal drain placement
- •Prior NEC or IP
- •Infant for whom full support is not being provided
- •Follow-up unlikely
结局指标
主要结局
Death or Neurodevelopmental Impairment (NDI)
时间窗: at 18-22 months corrected age
Death or NDI at 18-22 months corrected age
次要结局
- Death or Moderate to Severe Cerebral Palsy(up to the follow-up visit completed within the 18-22 months corrected age window)
- Death or Bayley Cognitive Composite Score Less Than 85(up to the follow-up visit completed within the 18-22 months corrected age window)
- Subsequent Laparotomy(between initial surgery and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Intraoperative Complications During Any Surgery(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Death(by 18-22 months corrected age)
- Survival With Neurodevelopmental Impairment (NDI)(by 18-22 months corrected age)
- Death or Blindness(up to the follow-up visit completed within the 18-22 months corrected age window)
- Any Severe IVH(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Death or Hearing Loss(up to the follow-up visit completed within the 18-22 months corrected age window)
- Any Intra-abdominal Abscess(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Final Bowel Length(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Duration of Mechanical Ventilation(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Duration of Parenteral Nutrition(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Time to Full Feeds(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis(by 18-22 months corrected age)
- Death or Hearing Loss Stratified by Pre-operative Diagnosis(up to the follow-up visit completed within the 18-22 months corrected age window)
- Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Late Onset Sepsis Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Wound Dehiscence(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Intestinal Stricture(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Length of Hospital Stay(from randomization up to 1 year following birth)
- Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis(up to the follow-up visit completed within the 18-22 months corrected age window)
- Subsequent Laparotomy Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Intestinal Stricture Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Length of Hospital Stay Stratified by Pre-operative Diagnosis(from randomization up to 1 year following birth)
- Any Late Onset Sepsis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Parenteral Nutrition (PN)-Associated Cholestasis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Death or NDI Stratified by Pre-operative Diagnosis(at 18-22 months corrected age)
- Death Stratified by Pre-operative Diagnosis(by 18-22 months corrected age)
- Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis(up to the follow-up visit completed within the 18-22 months corrected age window)
- Death or Blindness Stratified by Pre-operative Diagnosis(up to the follow-up visit completed within the 18-22 months corrected age window)
- Final Bowel Length Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Time to Full Feeds Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Wound Dehiscence Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Any Severe IVH Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)
- Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis(between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth)