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Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis (NEST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01029353
Recruitment Status : Completed
First Posted : December 10, 2009
Results First Posted : November 23, 2021
Last Update Posted : November 23, 2021
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Enterocolitis, Necrotizing Intestinal Perforation Procedure: Laparotomy Procedure: Drainage Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 529 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 2010
Actual Primary Completion Date : August 2019
Actual Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Randomized Trial: Laparotomy
Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.
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.

Active Comparator: Randomized Trial: Peritoneal drain placement
Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Procedure: Drainage
Initial drainage will involve placing a Penrose drain in the abdomen.
Other Name: Peritoneal drain

Active Comparator: Preference Cohort: Laparotomy
Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.
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.

Active Comparator: Preference Cohort: Peritoneal drain placement
Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Procedure: Drainage
Initial drainage will involve placing a Penrose drain in the abdomen.
Other Name: Peritoneal drain




Primary Outcome Measures :
  1. Death or Neurodevelopmental Impairment (NDI) [ Time Frame: at 18-22 months corrected age ]
    Death or NDI at 18-22 months corrected age


Secondary Outcome Measures :
  1. Death [ Time Frame: by 18-22 months corrected age ]
    Death by 18-22 months corrected age

  2. Survival With Neurodevelopmental Impairment (NDI) [ Time Frame: by 18-22 months corrected age ]
    NDI at 18-22 months corrected age (among survivors)

  3. Death or Moderate to Severe Cerebral Palsy [ Time Frame: 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

  4. Death or Bayley Cognitive Composite Score Less Than 85 [ Time Frame: 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.

  5. Death or Blindness [ Time Frame: 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

  6. Death or Hearing Loss [ Time Frame: 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

  7. Subsequent Laparotomy [ Time Frame: 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

  8. Any Intraoperative Complications During Any Surgery [ Time Frame: 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

  9. Any Wound Dehiscence [ Time Frame: 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

  10. Any Intra-abdominal Abscess [ Time Frame: 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

  11. Any Intestinal Stricture [ Time Frame: 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

  12. Any Late Onset Sepsis [ Time Frame: 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

  13. Any Parenteral Nutrition (PN)-Associated Cholestasis [ Time Frame: 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

  14. Any Severe IVH [ Time Frame: 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

  15. Duration of Mechanical Ventilation [ Time Frame: 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

  16. Duration of Parenteral Nutrition [ Time Frame: 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

  17. Final Bowel Length [ Time Frame: 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

  18. Time to Full Feeds [ Time Frame: 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

  19. Length of Hospital Stay [ Time Frame: from randomization up to 1 year following birth ]
    Length of hospital stay while on study

  20. Death or NDI Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  21. Death Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  22. Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  23. Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  24. Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis [ Time Frame: 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.

  25. Death or Blindness Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  26. Death or Hearing Loss Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  27. Subsequent Laparotomy Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  28. Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  29. Any Wound Dehiscence Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  30. Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  31. Any Intestinal Stricture Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  32. Any Late Onset Sepsis Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  33. Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  34. Any Severe IVH Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  35. Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  36. Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  37. Final Bowel Length Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  38. Time to Full Feeds Stratified by Pre-operative Diagnosis [ Time Frame: 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).

  39. Length of Hospital Stay Stratified by Pre-operative Diagnosis [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 8 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01029353


Locations
Show Show 22 study locations
Sponsors and Collaborators
NICHD Neonatal Research Network
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Investigators
Layout table for investigator information
Principal Investigator: Abbot R. Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: C. Michael Cotten, MD Duke University
Principal Investigator: David Carlton, MD Emory University
Principal Investigator: Greg Sokol, MD Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Ivan D. Frantz III, MD Tufts Medical Center
Principal Investigator: Brenda Poindexter, MD, MS Children's Hospital Medical Center, Cincinnati
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Edward F. Bell, MD University of Iowa
Principal Investigator: Kristi L. Watterberg, MD University of New Mexico
Principal Investigator: Myra Wyckoff, MD University of Texas, Southwestern Medical Center at Dallas
Principal Investigator: Kathleen A. Kennedy, MD MPH The University of Texas Health Science Center, Houston
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Study Director: Martin K. Blakely, MD Vanderbilt University Medical Center
Principal Investigator: William Truog, MD Children's Mercy Hospital Kansas City
Principal Investigator: Barbara Schmidt, MD, MSc Univeristy of Pennsylvania
Principal Investigator: Carl D'Angio, MD University of Rochester
Principal Investigator: Uday Devaskar, MD University of Carlifornia - Los Angeles
Principal Investigator: Leif Nelin, MD Research Institute at Nationwide Children's Hospital
Principal Investigator: Brad Yoder, MD University of Utah
  Study Documents (Full-Text)

Documents provided by NICHD Neonatal Research Network:
Study Protocol  [PDF] February 12, 2013
Statistical Analysis Plan  [PDF] August 23, 2019

Additional Information:
Layout table for additonal information
Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT01029353    
Other Study ID Numbers: NICHD-NRN-0039
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD036790 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
U10HD053089 ( U.S. NIH Grant/Contract )
U10HD053109 ( U.S. NIH Grant/Contract )
U10HD053119 ( U.S. NIH Grant/Contract )
U10HD053124 ( U.S. NIH Grant/Contract )
UL1RR024139 ( U.S. NIH Grant/Contract )
UL1RR025744 ( U.S. NIH Grant/Contract )
UL1RR025764 ( U.S. NIH Grant/Contract )
UL1RR025777 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
UL1RR024979 ( U.S. NIH Grant/Contract )
U10HD068284 ( U.S. NIH Grant/Contract )
U10HD068278 ( U.S. NIH Grant/Contract )
U10HD068270 ( U.S. NIH Grant/Contract )
U10HD068263 ( U.S. NIH Grant/Contract )
U10HD068244 ( U.S. NIH Grant/Contract )
UG1HD087226 ( U.S. NIH Grant/Contract )
First Posted: December 10, 2009    Key Record Dates
Results First Posted: November 23, 2021
Last Update Posted: November 23, 2021
Last Verified: November 2021
Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity
Laparotomy
Drainage
Isolated intestinal perforation
Focal intestinal perforation
Additional relevant MeSH terms:
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Enterocolitis
Enterocolitis, Necrotizing
Intestinal Perforation
Birth Weight
Body Weight
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases