Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis
- Conditions
- Infant, PrematureEnterocolitis, NecrotizingInfant, NewbornInfant, Low Birth WeightInfant, Small for Gestational AgeIntestinal Perforation
- Interventions
- Procedure: LaparotomyProcedure: Drainage
- Registration Number
- NCT01029353
- Lead Sponsor
- NICHD Neonatal Research Network
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 529
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomized Trial: Laparotomy Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Preference Cohort: Laparotomy Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Preference Cohort: Peritoneal drain placement Drainage Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Randomized Trial: Peritoneal drain placement Drainage Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
- Primary Outcome Measures
Name Time Method Death or Neurodevelopmental Impairment (NDI) at 18-22 months corrected age Death or NDI at 18-22 months corrected age
- Secondary Outcome Measures
Name Time Method Death or Hearing Loss up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age
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 Any intra-abdominal abscess during any surgery
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 Final bowel length after last surgery
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 mechanical ventilation while on study
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 Duration of parenteral nutrition while on study
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 Time to full feeds while on study
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis by 18-22 months corrected age NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Death or Hearing Loss Stratified by Pre-operative Diagnosis up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 wound dehiscence during any surgery
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 Any intestinal stricture during any surgery
Length of Hospital Stay from randomization up to 1 year following birth Length of hospital stay while on study
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 Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Length of Hospital Stay Stratified by Pre-operative Diagnosis from randomization up to 1 year following birth Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 late onset sepsis after randomization
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 Any Parenteral nutrition (PN)-associated cholestasis during any surgery
Death or NDI Stratified by Pre-operative Diagnosis at 18-22 months corrected age Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Death Stratified by Pre-operative Diagnosis by 18-22 months corrected age Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70.
Death or Blindness Stratified by Pre-operative Diagnosis up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or blindness at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
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 Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Death or Moderate to Severe Cerebral Palsy up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age
Death or Bayley Cognitive Composite Score Less Than 85 up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70.
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 Subsequent laparotomy after initial surgery
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 Any intraoperative complications during any surgery
Death by 18-22 months corrected age Death by 18-22 months corrected age
Survival With Neurodevelopmental Impairment (NDI) by 18-22 months corrected age NDI at 18-22 months corrected age (among survivors)
Death or Blindness up to the follow-up visit completed within the 18-22 months corrected age window Death within 18-22 months corrected age or blindness at 18-22 months corrected age
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 Any severe IVH ater randomization
Trial Locations
- Locations (22)
Emory University
🇺🇸Atlanta, Georgia, United States
Research Institute at Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Univeristy of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
University of Rochester
🇺🇸Rochester, New York, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of California - Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
RTI International
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States