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

Endeavor Health2 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Interventions

hydrocortisoneDRUG

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and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.

placeboDRUG

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.

Eligibility

Sex: ALLMin age: 0 DaysMax age: 6 Months

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

CRP Level

C-reactive protein is a non-specific marker of inflammation, noted to be elevated in infants diagnosed with NEC.

Time frame: 3 days

CRP Level

C-reactive protein (CRP) is a non-specific measure of inflammation, usually elevated in infants diagnosed with NEC

Time frame: 7 days

Secondary Outcomes

Gastrointestinal (GI) Failure (Defined as Not Being on Full Enteral Feeds of 120kcal/kg/Day at 36 Weeks Corrected Age)

GI failure

Time frame: 36 weeks corrected gestational age

Spontaneous Intestinal Perforation

Whether or not infants had perforation.

Time frame: at 36 weeks corrected gestational age

Need for Gastrointestinal Surgery

Whether or not the infants required GI surgery by 36 weeks CGA

Time frame: at 36 weeks corrected gestational age

Incidence of Sepsis

Whether or not enrolled subjects had sepsis before 40 weeks CGA