Trial Outcomes & Findings for Anti-inflammatory Treatment at the Onset of Necrotizing Enterocolitis (NEC) in Preterm Infants (NCT NCT01156480)

NCT ID: NCT01156480

Last Updated: 2020-09-09

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 2 participants
• Primary outcome timeframe: 3 days
• Results posted on: 2020-09-09

Participant Flow

Participant milestones

Measure	Hydrocortisone hydrocortisone group will receive 3mg/kg/day divided every 8 hours via intravenous route for 3 days, then 2mg/kg/day divided every 8 hours IV for 1 day, then 1.5mg/kg/day divided every 8 hours IV for 1 day, then 1mg/kg/day divided every 12 hours for 1 day, then 0.5mg/kg/day in single dose for one day. Placebo group will receive equal volume of placebo on the same schedule. The first dose of study drug will be given within 6 hours of NEC diagnosis, 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and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.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 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and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.
Overall Study STARTED	0	2
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Hydrocortisone hydrocortisone group will receive 3mg/kg/day divided every 8 hours via intravenous route for 3 days, then 2mg/kg/day divided every 8 hours IV for 1 day, then 1.5mg/kg/day divided every 8 hours IV for 1 day, then 1mg/kg/day divided every 12 hours for 1 day, then 0.5mg/kg/day in single dose for one day. Placebo group will receive equal volume of placebo on the same schedule. The first dose of study drug will be given within 6 hours of NEC diagnosis, 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and subjects will continue to receive study drug until all doses have been given (total of 18 doses) or consent is withdrawn.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 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.
Overall Study change in diagnosis	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	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.	Placebo n=1 Participants 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.	Total n=1 Participants Total of all reporting groups
Age, Categorical <=18 years	—	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	—	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	—	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 days

Population: This study was terminated due to low enrollment. We had a drop in our incidence of NEC, so there were very few eligible infants. One subject that was enrolled was soon thereafter thought NOT to have NEC, so that subject never received study drug.

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

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
CRP Level	—	25.3 mg/L

PRIMARY outcome

Timeframe: 7 days

Population: This study was terminated due to low enrollment. We had a drop in our incidence of NEC, so there were very few eligible infants. One subject that was enrolled was soon thereafter thought NOT to have NEC, so that subject never received study drug.

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

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
CRP Level	—	6.7 mg/L

SECONDARY outcome

Timeframe: 36 weeks corrected gestational age

Population: The one enrolled infant did not have GI failure at 36 weeks CGA.

GI failure

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Gastrointestinal (GI) Failure (Defined as Not Being on Full Enteral Feeds of 120kcal/kg/Day at 36 Weeks Corrected Age)	—	0 Participants

SECONDARY outcome

Timeframe: at 36 weeks corrected gestational age

Population: Only 1 infant enrolled (placebo group)

Whether or not infants had perforation.

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Spontaneous Intestinal Perforation	—	0 Participants

SECONDARY outcome

Timeframe: at 36 weeks corrected gestational age

Population: We only enrolled one subject (placebo group)

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

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Need for Gastrointestinal Surgery	—	0 Participants

SECONDARY outcome

Timeframe: at 40 weeks corrected gestational age

Population: We only enrolled one subject (placebo group). She did have fungal sepsis).

Whether or not enrolled subjects had sepsis before 40 weeks CGA

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Incidence of Sepsis	—	1 Participants

SECONDARY outcome

Timeframe: at 40 weeks corrected gestational age

Population: Only one subject was enrolled (placebo group)

Total time on parenteral nutrition

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Time on Parenteral Nutrition	—	39 days

SECONDARY outcome

Timeframe: at 40 weeks corrected gestational age

Population: We only enrolled one subject into the placebo group.

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

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Time to Full Enteral Feeds	—	35 days

SECONDARY outcome

Timeframe: at 40 weeks corrected gestational age

Population: only one subject enrolled into placebo group

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.

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Length of Stay	—	141 days

SECONDARY outcome

Timeframe: at 40 weeks CGA

Population: We only enrolled one subject into the placebo group.

Growth velocity after NEC diagnosis, in g/kg/day.

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Growth Velocity	—	14.4 grams/kg/d

SECONDARY outcome

Timeframe: at 40 weeks corrected gestational age

Population: Only one subject was enrolled into the placebo group.

Outcome measures

Measure	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.	Placebo n=1 Participants 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.
Mortality	—	0 Participants

Adverse Events

Hydrocortisone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Brandy Frost

NorthShore University HealthSystem

Phone: 847-570-2033

Email: bfrost@northshore.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place