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

Purpose

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.

Condition	Intervention
Necrotizing Enterocolitis	Drug: hydrocortisone Drug: placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Anti-inflammatory Treatment at the Onset of NEC in Preterm Infants- a Pilot Study

Resource links provided by NLM:

MedlinePlus related topics: Premature Babies

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Hydrocortisone butyrate Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by NorthShore University HealthSystem Research Institute:

Primary Outcome Measures:

CRP level [ Time Frame: 3 days ] [ Designated as safety issue: No ]
CRP level [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

gastrointestinal (GI) failure (defined as not being on full enteral feeds of 120kcal/kg/day at 36 weeks corrected age) [ Time Frame: 36 weeks corrected gestational age ] [ Designated as safety issue: No ]
spontaneous intestinal perforation [ Time Frame: at 36 weeks corrected gestational age ] [ Designated as safety issue: Yes ]
need for gastrointestinal surgery [ Time Frame: at 36 weeks corrected gestational age ] [ Designated as safety issue: No ]
incidence of sepsis [ Time Frame: at 40 weeks corrected gestational age ] [ Designated as safety issue: Yes ]
time on parenteral nutrition [ Time Frame: at 40 weeks corrected gestational age ] [ Designated as safety issue: No ]
time to full enteral feeds [ Time Frame: at 40 weeks corrected gestational age ] [ Designated as safety issue: No ]
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
length of stay [ Time Frame: at 40 weeks CGA ] [ Designated as safety issue: No ]
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 CGA, however, so these infants will need to have length of stay assessed later than 40 weeks CGA.
growth velocity [ Time Frame: at 40 weeks CGA ] [ Designated as safety issue: No ]
mortality [ Time Frame: at 40 weeks corrected gestational age ] [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	September 2009
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study:	up to 6 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01156480

Contacts

Contact: Brandy L Frost, MD	847-570-2033	bfrost@northshore.org
Contact: Michael S Caplan, MD	847-570-2033	mcaplan@northshore.org

Locations

United States, Illinois
University of Chicago Comer Childrens Hospital	Recruiting
Chicago, Illinois, United States
NorthShore University HealthSystem	Recruiting
Evanston, Illinois, United States, 60201
Contact: Brandy L Frost, MD 847-570-2033 bfrost@northshore.org
Principal Investigator: Brandy L Frost, MD

Sponsors and Collaborators

NorthShore University HealthSystem Research Institute

University of Chicago

Investigators

Principal Investigator:

Brandy L Frost, MD

NorthShore University HealthSystem

More Information

No publications provided

Responsible Party:	Brandy Frost, MD, NorthShore University HealthSystem
ClinicalTrials.gov Identifier:	NCT01156480 History of Changes
Other Study ID Numbers:	EH09-196
Study First Received:	July 1, 2010
Last Updated:	July 11, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by NorthShore University HealthSystem Research Institute:

necrotizing enterocolitis
NEC
premature

hydrocortisone
steroids
anti-inflammatory

Additional relevant MeSH terms:

Enterocolitis
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Cortisol succinate
Hydrocortisone acetate

Hydrocortisone 17-butyrate 21-propionate
Anti-Inflammatory Agents
Hydrocortisone
Hydrocortisone-17-butyrate
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on May 16, 2013

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