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

This study has been terminated.
(low enrollment)
Sponsor:
Collaborator:
University of Chicago
Information provided by (Responsible Party):
Brandy Frost, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier:
NCT01156480
First received: July 1, 2010
Last updated: April 15, 2014
Last verified: April 2014
  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:


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

  • CRP Level [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    C-reactive protein (CRP) is a non-specific measure of inflammation, usually elevated in infants diagnosed with NEC


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 corrected gestational age ] [ 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 corrected gestational age (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 ]

Enrollment: 2
Study Start Date: September 2009
Study Completion Date: November 2012
Primary Completion Date: November 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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Illinois
University of Chicago Comer Childrens Hospital
Chicago, Illinois, United States
NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
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, Clinician Educator and Attending Neonatologist, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier: NCT01156480     History of Changes
Other Study ID Numbers: EH09-196
Study First Received: July 1, 2010
Results First Received: January 8, 2014
Last Updated: April 15, 2014
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
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Anti-Inflammatory Agents
Hydrocortisone
Hydrocortisone-17-butyrate
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on August 26, 2014