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

Not Applicable

Terminated

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	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.
hydrocortisone	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.

Primary Outcome Measures

Name	Time	Method
CRP Level	7 days	C-reactive protein (CRP) is a non-specific measure of inflammation, usually elevated in infants diagnosed with NEC

Secondary Outcome Measures

Name	Time	Method
Spontaneous Intestinal Perforation	at 36 weeks corrected gestational age	Whether or not infants had perforation.
Time on Parenteral Nutrition	at 40 weeks corrected gestational age	Total time on parenteral nutrition
Time to Full Enteral Feeds	at 40 weeks corrected gestational age	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
Need for Gastrointestinal Surgery	at 36 weeks corrected gestational age	Whether or not the infants required GI surgery by 36 weeks CGA
Growth Velocity	at 40 weeks CGA	Growth velocity after NEC diagnosis, in g/kg/day.
Mortality	at 40 weeks corrected gestational age
Gastrointestinal (GI) Failure (Defined as Not Being on Full Enteral Feeds of 120kcal/kg/Day at 36 Weeks Corrected Age)	36 weeks corrected gestational age	GI failure
Incidence of Sepsis	at 40 weeks corrected gestational age	Whether or not enrolled subjects had sepsis before 40 weeks CGA
Length of Stay	at 40 weeks corrected gestational age	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.

Locations (2): NorthShore University HealthSystem
🇺🇸
Evanston, Illinois, United States
University of Chicago Comer Childrens Hospital
🇺🇸
Chicago, Illinois, United States