Trial Outcomes & Findings for Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants (NCT NCT00167544)

NCT ID: NCT00167544

Last Updated: 2013-08-30

Results Overview

Total cerebral volume included all brain gray matter and white matter, including cerebellum.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: 38 weeks postmenstrual age (PMA)
• Results posted on: 2013-08-30

Participant Flow

All extremely low birth weight infants (ELBW; birth weight <=1000g) that were mechanically ventilated between day of life 10 to 21 were screened for eligibility in the neonatal intensive care unit at Children's Memorial Hermann Hospital during the period of October 11, 2005 and September 8, 2008.

Parent/guardian was approached if infant's respiratory index score (mean airway pressure x FiO2) was ≥ 2.0 and stable or increasing or if the respiratory index score was ≥ 3.0 when improvement was noted in the previous 24 hour period.

Participant milestones

Measure	Hydrocortisone Arm Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Overall Study STARTED	31	33
Overall Study COMPLETED	30	33
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

Baseline characteristics by cohort

Measure	Hydrocortisone Arm n=31 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	31 Participants n=5 Participants	33 Participants n=7 Participants	64 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	25 weeks INTER_QUARTILE_RANGE 3 • n=5 Participants	25 weeks INTER_QUARTILE_RANGE 3 • n=7 Participants	25 weeks INTER_QUARTILE_RANGE 3 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	20 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	33 participants n=7 Participants	64 participants n=5 Participants

PRIMARY outcome

Timeframe: 38 weeks postmenstrual age (PMA)

Population: Eight infants died in each group prior to term MRI precluding a determination of brain volumes. Additionally, four infants had poor quality MRI scans that could not be analyzed for brain volumes.

Total cerebral volume included all brain gray matter and white matter, including cerebellum.

Outcome measures

Measure	Hydrocortisone Arm n=23 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=21 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Total Cerebral Volume as Measured by Volumetric Brain MRI	272.01 cm^3 Standard Deviation 40.30	277.82 cm^3 Standard Deviation 59.05

SECONDARY outcome

Timeframe: 38-weeks postmenstrual age

Population: In addition to the reasons cited for the primary outcome, one infant in the hydrocortisone group and two in the placebo group had artifacts on brain MRI precluding cerebral white matter segmentation and volume determination.

Cerebral white matter volume

Outcome measures

Measure	Hydrocortisone Arm n=22 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=19 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Regional Brain Volumes	122.45 cm^3 Standard Deviation 18.73	118.62 cm^3 Standard Deviation 17.51

SECONDARY outcome

Timeframe: Up to 36 weeks PMA

Outcome measures

Measure	Hydrocortisone Arm n=31 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure)	68.7 days Interval 63.4 to 74.0	65.9 days Interval 59.7 to 72.0

SECONDARY outcome

Timeframe: Up to 36 weeks PMA

Outcome measures

Measure	Hydrocortisone Arm n=31 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Duration of Oxygen Requirement	72.7 days Interval 68.0 to 77.4	72.0 days Interval 66.9 to 77.1

SECONDARY outcome

Timeframe: 36 weeks postmenstrual age

Using the NIH Consensus definition (Jobe A, 2001)

Outcome measures

Measure	Hydrocortisone Arm n=31 Participants Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 Participants Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Survival Without Severe Bronchopulmonary Dysplasia (BPD)	3 participants	5 participants

Adverse Events

Hydrocortisone Arm

Serious events: 8 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Hydrocortisone Arm n=31 participants at risk Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 participants at risk Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Cardiac disorders Death before NICU discharge	25.8% 8/31 • Number of events 8	24.2% 8/33 • Number of events 8

Other adverse events

Measure	Hydrocortisone Arm n=31 participants at risk Subjects randomized by the investigational drug pharmacist to hydrocortisone arm received a 7 day course of intravenous (IV) hydrocortisone sodium succinate (Solu-Cortef) every 12 hours (3 mg/kg per day for first 4 days, 2 mg/kg per day for 2 days and 1 mg/kg per day for 1 day; total of 17 mg/kg over 7 days). The IV route was preferred.	Placebo Arm n=33 participants at risk Subjects randomized by the investigational drug pharmacist to the placebo arm received an equivalent volume of identical appearing 0.9% sterile saline placebo. The IV route was preferred.
Gastrointestinal disorders Spontaneous intestinal perforation	6.5% 2/31 • Number of events 2	0.00% 0/33

Additional Information

Dr. Nehal Parikh

Nationwide Children's Hospital Clinical Research Institute

Phone: 614-355-6657

Email: nehal.parikh@nationwidechildrens.org

Results disclosure agreements

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