Anti-inflammatory Treatment at the Onset of Necrotizing Enterocolitis (NEC) in Preterm Infants (steroids/NEC)

Anti-inflammatory Treatment at the Onset of NEC in Preterm Infants- a Pilot Study

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant problem in neonatal intensive care units (ICUs). Although research has shown NEC to be an inflammatory necrosis of the bowels, to date no study has examined the effect of anti-inflammatory therapy on this dreaded disease once it is diagnosed. The investigators propose a multi-center, randomized, placebo-controlled, double-blinded pilot study to examine the effect of hydrocortisone in infants diagnosed with stages II and III NEC. The investigators will follow C-reactive protein (CRP) levels as a marker of systemic inflammation for the primary outcome in this study.

Study Overview

• Status: Terminated
• Conditions: Necrotizing Enterocolitis
• Intervention / Treatment: Drug: hydrocortisone; Drug: placebo

Detailed Description

Given the extensive inflammatory response inherent to NEC, anti-inflammatory treatment may be of benefit, to both reduce inflammation and as a potential therapy to improve outcome. To date, there is no specific therapy for NEC that has been found to improve outcome, but corticosteroids have yet to be investigated in that capacity. Therefore, we propose to examine the effect of hydrocortisone for treatment of NEC in a randomized, blinded, placebo-controlled pilot study, focusing on a primary outcome of C-reactive protein levels at 3 and 7 days of therapy as a measure of inflammation. In addition, we will follow several secondary outcome measures to determine the possibility of improved outcome in those infants assigned to hydrocortisone.

The investigators hypothesize that infants diagnosed with NEC who receive hydrocortisone will have significantly lower C-reactive protein levels at 3 and 7 days of treatment versus infants who receive placebo.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago Comer Childrens Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University Healthsystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infant born at gestational age less than 34 weeks
• Birth weight less than 2500 grams
• Diagnosis of stage II or III NEC made by attending neonatologist, neonatology fellow, or pediatric hospitalist
• Legally authorized representative is able to provide written informed consent prior to the performance of an protocol-specified evaluations or procedures
• Consent can be obtained and study drug can be administered within 6 hours of diagnosis

Exclusion Criteria:

• congenital gastrointestinal anomaly
• subject is already receiving parenteral steroid therapy or subject has received parenteral steroids within one week prior to study entry
• subject has received indomethacin therapy within 48 hours prior to being diagnosed with NEC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hydrocortisone; Subjects in hydrocortisone group will receive 3mg/kg/day divided every 8 hours via intravenous (IV) route for 3 days, followed by 2mg/kg/day divided every 8 hours IV for 1 day, followed by 1.5mg/kg/day divided every 8 hours IV for 1 day, followed by 1mg/kg/day divided every 12 hours for 1 day, followed by 0.5mg/kg/day in single dose for one day. Subjects in placebo group will receive equal volume of placebo on the same dosing schedule. The first dose of study drug will be given within 6 hours of diagnosis of NEC, once informed consent is obtained, and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.	Drug: hydrocortisone; Subjects in hydrocortisone group will receive 3mg/kg/day divided every 8 hours via IV route for 3 days, followed by 2mg/kg/day divided every 8 hours IV for 1 day, followed by 1.5mg/kg/day divided every 8 hours IV for 1 day, followed by 1mg/kg/day divided every 12 hours for 1 day, followed by 0.5mg/kg/day in single dose for one day. The first dose of study drug will be given within 6 hours of diagnosis of NEC, once informed consent is obtained, and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.
Placebo Comparator: Placebo; Subjects in placebo group will receive equal volume of placebo (as compared to hydrocortisone arm) on the same dosing schedule. The first dose of study drug will be given within 6 hours of diagnosis of NEC, once informed consent is obtained, and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.	Drug: placebo; Subjects in placebo group will receive a volume of placebo equal to the hydrocortisone group, on the same dosing schedule, with doses given every 8 hours via IV route for 3 days, followed by placebo every 8 hours IV for 1 day, followed by placebo every 8 hours IV for 1 day, followed by placebo every 12 hours for 1 day, followed by placebo in single dose for one day. The first dose of study drug will be given within 6 hours of diagnosis of NEC, once informed consent is obtained, and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRP Level	C-reactive protein is a non-specific marker of inflammation, noted to be elevated in infants diagnosed with NEC.	3 days
CRP Level	C-reactive protein (CRP) is a non-specific measure of inflammation, usually elevated in infants diagnosed with NEC	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal (GI) Failure (Defined as Not Being on Full Enteral Feeds of 120kcal/kg/Day at 36 Weeks Corrected Age)	GI failure	36 weeks corrected gestational age
Spontaneous Intestinal Perforation	Whether or not infants had perforation.	at 36 weeks corrected gestational age
Need for Gastrointestinal Surgery	Whether or not the infants required GI surgery by 36 weeks CGA	at 36 weeks corrected gestational age
Incidence of Sepsis	Whether or not enrolled subjects had sepsis before 40 weeks CGA	at 40 weeks corrected gestational age
Time on Parenteral Nutrition	Total time on parenteral nutrition	at 40 weeks corrected gestational age
Time to Full Enteral Feeds	this will be assessed as the time needed to achieve full enteral feeds following the diagnosis of NEC. On average, it will be assessed at 40 weeks CGA, near the time of discharge, but there is a subset of infants who will not yet have achieved full enteral feeds at that time, so it may need to be assessed later than 40 weeks CGA	at 40 weeks corrected gestational age
Length of Stay	this will be assessed at the time of discharge, around 40 weeks CGA on average. A subset of infants may be discharged later than 40 weeks corrected gestational age (CGA), however, so these infants will need to have length of stay assessed later than 40 weeks CGA.	at 40 weeks corrected gestational age
Growth Velocity	Growth velocity after NEC diagnosis, in g/kg/day.	at 40 weeks CGA
Mortality		at 40 weeks corrected gestational age

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Collaborators: University of Chicago
• Investigators: Principal Investigator: Brandy L Frost, MD, NorthShore University Healthsystem

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: July 1, 2010
• First Submitted That Met QC Criteria: July 1, 2010
• First Posted (Estimate): July 2, 2010

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: anti-inflammatory; premature; necrotizing enterocolitis; hydrocortisone; steroids; NEC
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: EH09-196