Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis

Infant, Premature Clinical Trial

— NEST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01029353
• Other study ID #: NICHD-NRN-0039
• Secondary ID: U10HD021364U10HD
• Status: Completed
• Phase: N/A
• Start date: January 2010
• Est. completion date: August 2019

Study information

• Verified date: November 2021
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 529
• Est. completion date: August 2019
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 8 Weeks

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Birth Weight
• Enterocolitis
• Enterocolitis, Necrotizing
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age
• Intestinal Perforation

Intervention

Procedure:
• Laparotomy
Initial laparotomy will be performed. Standard procedures will be used, including inspection of the bowel with removal of diseased areas, creation of stoma(s), and other procedures deemed indicated by the surgeon.
• Drainage
Initial drainage will involve placing a Penrose drain in the abdomen.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of California - Los Angeles	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Univeristy of Pennsylvania	Philadelphia	Pennsylvania
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or Neurodevelopmental Impairment (NDI)	Death or NDI at 18-22 months corrected age	at 18-22 months corrected age
Secondary	Death	Death by 18-22 months corrected age	by 18-22 months corrected age
Secondary	Survival With Neurodevelopmental Impairment (NDI)	NDI at 18-22 months corrected age (among survivors)	by 18-22 months corrected age
Secondary	Death or Moderate to Severe Cerebral Palsy	Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Bayley Cognitive Composite Score Less Than 85	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.	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Blindness	Death within 18-22 months corrected age or blindness at 18-22 months corrected age	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Hearing Loss	Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Subsequent Laparotomy	Subsequent laparotomy after initial surgery	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
Secondary	Any Intraoperative Complications During Any 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
Secondary	Any Wound Dehiscence	Any wound dehiscence 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
Secondary	Any Intra-abdominal Abscess	Any intra-abdominal abscess 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
Secondary	Any Intestinal Stricture	Any intestinal stricture 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
Secondary	Any Late Onset Sepsis	Any late onset sepsis after randomization	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Parenteral Nutrition (PN)-Associated Cholestasis	Any Parenteral nutrition (PN)-associated cholestasis 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
Secondary	Any Severe IVH	Any severe IVH ater randomization	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Duration of Mechanical Ventilation	Duration of mechanical ventilation while on study	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Duration of Parenteral Nutrition	Duration of parenteral nutrition while on study	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Final Bowel Length	Final bowel length after last 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
Secondary	Time to Full Feeds	Time to full feeds while on study	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Length of Hospital Stay	Length of hospital stay while on study	from randomization up to 1 year following birth
Secondary	Death or NDI Stratified by Pre-operative Diagnosis	Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	at 18-22 months corrected age
Secondary	Death Stratified by Pre-operative Diagnosis	Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	by 18-22 months corrected age
Secondary	Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis	NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	by 18-22 months corrected age
Secondary	Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis	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).	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis	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.	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Blindness Stratified by Pre-operative Diagnosis	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).	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Death or Hearing Loss Stratified by Pre-operative Diagnosis	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).	up to the follow-up visit completed within the 18-22 months corrected age window
Secondary	Subsequent Laparotomy Stratified by Pre-operative Diagnosis	Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis	Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Wound Dehiscence Stratified by Pre-operative Diagnosis	Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis	Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Intestinal Stricture Stratified by Pre-operative Diagnosis	Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Late Onset Sepsis Stratified by Pre-operative Diagnosis	Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis	Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Any Severe IVH Stratified by Pre-operative Diagnosis	Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis	Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis	Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Final Bowel Length Stratified by Pre-operative Diagnosis	Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Time to Full Feeds Stratified by Pre-operative Diagnosis	Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Length of Hospital Stay Stratified by Pre-operative Diagnosis	Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).	from randomization up to 1 year following birth

External Links

•   NICHD Neonatal Research Network