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Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

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ClinicalTrials.gov Identifier: NCT00167544
Recruitment Status : Completed
First Posted : September 14, 2005
Results First Posted : August 30, 2013
Last Update Posted : August 30, 2013
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Nehal Parikh, Nationwide Children's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Bronchopulmonary Dysplasia
Encephalomalacia
Premature Birth
Interventions Drug: Hydrocortisone
Drug: Placebo
Enrollment 64
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 31 33
Completed 30 33
Not Completed 1 0
Arm/Group Title Hydrocortisone Arm Placebo Arm Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 31 33 64
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 33 participants 64 participants
<=18 years
31
 100.0%
33
 100.0%
64
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Weeks
Number Analyzed 31 participants 33 participants 64 participants
25
(24 to 26)
25
(24 to 27)
25
(24 to 27)
[1]
Measure Description: Gestational age
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 33 participants 64 participants
Female
17
  54.8%
13
  39.4%
30
  46.9%
Male
14
  45.2%
20
  60.6%
34
  53.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 31 participants 33 participants 64 participants
31 33 64
1.Primary Outcome
Title Total Cerebral Volume as Measured by Volumetric Brain MRI
Hide Description Total cerebral volume included all brain gray matter and white matter, including cerebellum.
Time Frame 38 weeks postmenstrual age (PMA)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 23 21
Mean (Standard Deviation)
Unit of Measure: cm^3
272.01  (40.30) 277.82  (59.05)
2.Secondary Outcome
Title Regional Brain Volumes
Hide Description Cerebral white matter volume
Time Frame 38-weeks postmenstrual age
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: cm^3
122.45  (18.73) 118.62  (17.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydrocortisone Arm, Placebo Arm
Comments The primary analysis of total brain tissue volume was performed using multiple linear regression controlling for postmenstrual age at MRI scan to adjust for differences in timing at MRI. The distributions of potentially important confounding variables at baseline were compared in the two groups using parametric and non-parametric tests as appropriate. All analyses were performed using STATA 11.0. Please see PubMed: 23140612.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.40
Confidence Interval (2-Sided) 95%
-19.49 to 30.29
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure)
Hide Description [Not Specified]
Time Frame Up to 36 weeks PMA
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 31 33
Mean (95% Confidence Interval)
Unit of Measure: days
68.7
(63.4 to 74.0)
65.9
(59.7 to 72.0)
4.Secondary Outcome
Title Duration of Oxygen Requirement
Hide Description [Not Specified]
Time Frame Up to 36 weeks PMA
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 31 33
Mean (95% Confidence Interval)
Unit of Measure: days
72.7
(68.0 to 77.4)
72.0
(66.9 to 77.1)
5.Secondary Outcome
Title Survival Without Severe Bronchopulmonary Dysplasia (BPD)
Hide Description Using the NIH Consensus definition (Jobe A, 2001)
Time Frame 36 weeks postmenstrual age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 31 33
Measure Type: Number
Unit of Measure: participants
3 5
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hydrocortisone Arm Placebo Arm
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Hydrocortisone Arm Placebo Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Hydrocortisone Arm Placebo Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/31 (25.81%)      8/33 (24.24%)    
Cardiac disorders     
Death before NICU discharge   8/31 (25.81%)  8 8/33 (24.24%)  8
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Hydrocortisone Arm Placebo Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/31 (6.45%)      0/33 (0.00%)    
Gastrointestinal disorders     
Spontaneous intestinal perforation   2/31 (6.45%)  2 0/33 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Nehal Parikh
Organization: Nationwide Children's Hospital Clinical Research Institute
Phone: 614-355-6657
EMail: nehal.parikh@nationwidechildrens.org
Layout table for additonal information
Responsible Party: Nehal Parikh, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT00167544     History of Changes
Other Study ID Numbers: K23NS048152 ( U.S. NIH Grant/Contract )
K23NS048152 ( U.S. NIH Grant/Contract )
HSC-MS-05-0218
First Submitted: September 9, 2005
First Posted: September 14, 2005
Results First Submitted: March 25, 2013
Results First Posted: August 30, 2013
Last Update Posted: August 30, 2013