Clinical trial NCT01029353: Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Enterocolitis, Necrotizing
Intestinal Perforation
Keywords: NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity
Laparotomy
Drainage
Isolated intestinal perforation
Focal intestinal perforation
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Research Resources (NCRR)
First posted: 2009-12-10
Enrollment: 529
Sex: ALL
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Death or Neurodevelopmental Impairment (NDI)
timeFrame: at 18-22 months corrected age
Secondary outcomes:
measure: Death
timeFrame: by 18-22 months corrected age
measure: Survival With Neurodevelopmental Impairment (NDI)
timeFrame: by 18-22 months corrected age
measure: Death or Moderate to Severe Cerebral Palsy
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Bayley Cognitive Composite Score Less Than 85
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Blindness
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Hearing Loss
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Subsequent Laparotomy
timeFrame: 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
measure: Any Intraoperative Complications During Any Surgery
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Wound Dehiscence
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Intra-abdominal Abscess
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Intestinal Stricture
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Late Onset Sepsis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Parenteral Nutrition (PN)-Associated Cholestasis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Severe IVH
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Duration of Mechanical Ventilation
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Duration of Parenteral Nutrition
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Final Bowel Length
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Time to Full Feeds
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Length of Hospital Stay
timeFrame: from randomization up to 1 year following birth
measure: Death or NDI Stratified by Pre-operative Diagnosis
timeFrame: at 18-22 months corrected age
measure: Death Stratified by Pre-operative Diagnosis
timeFrame: by 18-22 months corrected age
measure: Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis
timeFrame: by 18-22 months corrected age
measure: Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Blindness Stratified by Pre-operative Diagnosis
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Death or Hearing Loss Stratified by Pre-operative Diagnosis
timeFrame: up to the follow-up visit completed within the 18-22 months corrected age window
measure: Subsequent Laparotomy Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Wound Dehiscence Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Intestinal Stricture Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Late Onset Sepsis Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Any Severe IVH Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Final Bowel Length Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Time to Full Feeds Stratified by Pre-operative Diagnosis
timeFrame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Length of Hospital Stay Stratified by Pre-operative Diagnosis
timeFrame: from randomization up to 1 year following birth
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Univeristy of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: Abbot R. Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
name: Michele C. Walsh, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: C. Michael Cotten, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: David Carlton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Greg Sokol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa P. Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Ivan D. Frantz III, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Brenda Poindexter, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Edward F. Bell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi L. Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Myra Wyckoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Kathleen A. Kennedy, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Martin K. Blakely, MD
role: STUDY_DIRECTOR
affiliation: Children's Mercy Hospital Kansas City
name: William Truog, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univeristy of Pennsylvania
name: Barbara Schmidt, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Carl D'Angio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Carlifornia - Los Angeles
name: Uday Devaskar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute at Nationwide Children's Hospital
name: Leif Nelin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Brad Yoder, MD
role: PRINCIPAL_INVESTIGATOR
References: