Bronchopulmonary Dysplasia, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Infant, Very Low Birth Weight
Conditions
Keywords
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Very Low Birth Weight (VLBW), Prematurity, Mechanical ventilation, Intubation, Neurodevelopmental impairment
Brief summary
The Hydrocortisone and Extubation study will test the safety and efficacy of a 10 day course of hydrocortisone for infants who are less than 30 weeks estimated gestational age and who are intubated at 14-28 days of life. Infants will be randomized to receive hydrocortisone or placebo. This study will determine if hydrocortisone improves infants'survival without moderate or severe BPD and will be associated with improvement in survival without moderate or severe neurodevelopmental impairment at 22 - 26 months corrected age.
Detailed description
Bronchopulmonary dysplasia (BPD) remains a leading morbidity of the extremely preterm infant, and prolonged mechanical ventilation is associated with increased risk for BPD. Dexamethasone has been used previously to facilitate extubation and decrease the incidence of BPD; however, due to adverse effects on neurodevelopmental outcomes, the use of this drug has decreased. One cohort study suggests that hydrocortisone (HC) may facilitate extubation. HC has thus far not been associated with adverse neurodevelopmental outcomes in either cohort studies or randomized controlled trials. A recent meta-analysis of postnatal corticosteroid therapy begun after the first week of life suggested that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes, although the methodological quality of some of the follow-up was acknowledged to be limited. This is a randomized controlled trial to study the efficacy and safety of a 10-day tapering course of hydrocortisone treatment for infants \<30 weeks estimated gestational age at birth who remain intubated at 14 - 28 days postnatal age. Based on previous Network data these criteria define a population with a risk of death or BPD at 36 weeks postmenstrual age of approximately 65 - 75%. The primary outcome for this study will incorporate both (1) survival without moderate to severe BPD by Network physiologic definition and (2) survival without moderate or severe NDI at 18 - 22 months corrected age. Therefore, the results of this study will be reported only when follow-up data are available unless (1) the trial is stopped early by the DSMC because of strong evidence of benefit or harm, or (2) at the time all subjects have completed treatment the DCC finds a substantial survival benefit favoring hydrocortisone (p\<0.001). Individual study assignment will remain masked until the follow-up is completed. Secondary outcomes will include short term measures such as respiratory morbidities and growth at 36 weeks postmenstrual age and long term measures including growth and other outcomes at 22 - 26 months corrected age. Secondary studies include: 1. Effect of Hydrocortisone on the Cardiac mass of Premature Intubated Infants - will determine left ventricular mass index at 36 weeks postmenstrual age (or prior to discharge/transfer if after 34 weeks) in infants enrolled in the hydrocortisone for BPD RCT, and compare HC-treated infants to placebo-treated infants. It will similarly assess and compare the incidence of pulmonary hypertension in these patients. 2. Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to assess functional developmental and respiratory outcomes at early school age. In a subset of five Neonatal Research Network Clinical Centers, impulse oscillometry (IOS), which is the optimal direct measure of lung capacity and function, will be performed to validate the 6-minute walk test and International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire as functional measures of pulmonary status. Also at these five Centers, the six minute walk test, ISAAAC questionnaire, and IOS will be administered as part of (1) the Healthy Lungs sub-study, which will recruit 120 TOP 5 study participants who had minimal lung disease when they were infants to define normative ranges in healthy, preterm-born children, and (2) the Healthy Lungs Two sub-study, which will recruit 120 healthy, term-born children without history of lung disease to characterize functional and mechanical respiratory outcomes at 5-7 years of age.
Interventions
DRUGHydrocortisone
Hydrocortisone sodium succinate for intravenous administration (unpreserved, Solu-Cortef plain, Pfizer®, reconstituted with unpreserved normal saline to avoid exposure to the benzyl alcohol contained in preserved diluents), to be administered either intravenously or orally if no intravenous line is available at the same dose, and tapered as follows: 4mg/kg/day ¸ q 6 hours x 2 days, then 2mg/kg/day ¸ q 6 hours x 3 days; then 1mg/kg/day ¸ q 12 hours x 3 days; then 0.5mg/kg/d as a single dose x 2 days
DRUGPlacebo
Saline placebo to be administered either intravenously or orally if no intravenous line is available, at the same dose, and tapered as follows: 4mg/kg/day ¸ q 6 hours x 2 days, then 2mg/kg/day ¸ q 6 hours x 3 days; then 1mg/kg/day ¸ q 12 hours x 3 days; then 0.5mg/kg/d as a single dose x 2 days
Sponsors
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Advancing Translational Sciences (NCATS)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Weeks
Healthy volunteers
No
Inclusion criteria
* infants \<30 weeks estimated gestational age * inborn at an NRN site or were admitted to an NRN site before 72 hours postnatal age * have received at least 7days of mechanical ventilation; * are receiving mechanical ventilation through an endotracheal tube .
Exclusion criteria
* Major congenital anomalies * Decision to limit support * Indomethacin or ibuprofen treatment within 48 hours of study drug * Previous corticosteroid treatment for BPD * Received hydrocortisone for 14 or more cumulative days * Received hydrocortisone within 7 days of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD) | From day of randomization to 36 weeks post menstrual age | Survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. Moderate or severe physiologic BPD is defined as a requirement for supplemental oxygen and/or positive airway pressure to maintain oxygen saturation greater than 90 percent. A room air challenge was performed for infants estimated to be receiving less than 0.30 FiO2 by nasal cannula. |
| Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI) | From day of randomization to 22-26 months corrected age | Survival without moderate or severe neurodevelopmental impairment (NDI) at 22-26 months corrected age. NDI is defined as defined as any of: Bayley Scales of Infant and Toddler Development-III (Bayley-III) cognitive composite score less than 85 (standardized mean 100, SD 15, range 55-145) or motor composite score less than 85 (standardized mean 100, range 45-155) (lower scores indicating greater impairment), Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment), severe vision impairment in both eyes (consistent with refraction from less than 20 to 200), or bilateral hearing impairment with or without amplification (by report). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | At 36 weeks postmenstrual age | BPD grade at 36 weeks postmenstrual age. BPD grades are defined as: 1. No support/room air; 2. Nasal cannula (NC) O2 less than or equal to 2L; 3. NC O2 greater than 2L or CPAP/NIPPV; 4. Invasive PPV |
| Days of Mechanical Ventilation to 36 Weeks Postmenstrual Age (PMA) | From birth to 36 weeks postmenstrual age | Number of days on mechanical ventilation (using high frequency ventilator or conventional ventilator) |
| Duration of Oxygen Supplementation up to Status | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of days of oxygen supplementation from birth to discharge home |
| Length of Hospital Stay in Days Among Survivors to Discharge | From birth up to one year | Number of days infant stayed in hospitals, among those who survived to discharge |
| Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA) | From birth to 36 weeks postmenstrual age | Infant received dexamethasone anytime before 36 weeks postmenstrual age. |
| Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | At 22-26 months corrected age | Severity of neurodevelopmental impairment, defined as one or more of: Bayley Scales of Infant Development-III (Bayley-III) cognitive score \<85 (standardized mean 100, SD 15, range 55-145), Bayley-III motor score \<85 (standardized mean 100, range 45-155), Gross Motor Function Classification System (GMFCS) level ≥2, severe vision impairment in both eyes (consistent with refraction \<20-200), or bilateral hearing impairment with or without amplification (by report). Bayley-III = Bayley Scales of Infant Development III (Cognitive score standardized mean 100, SD 15, range 55-145 motor score standardized mean 100, range 45-155; higher score indicates better performance (20)) |
| Number of Participants With Gross Motor Function Greater Than or Equal to Level 2 | At 22-26 months corrected age | Number of infants with Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment) |
| Number of Participants With Moderate-severe Cerebral Palsy | At 22-26 months corrected age | Number of infants with moderate or severe grade of cerebral palsy. Cerebral Palsy was diagnosed when there were definite abnormalities observed in the neuromotor exam, and functional challenges as classified by GMFCS level, and classified as moderate if GMFCS level was II or III and severe if level IV or V (40). |
| Number of Participants With Severe Hearing Impairment (by Report) | At 22-26 months corrected age | Number of infants with bilateral hearing impairment with or without amplification (by report) |
| Number of Participants With no/Some Functional Vision | At 22-26 months corrected age | Number of infants with severe vision impairment in both eyes (consistent with refraction less than 20-200) |
| Weight Growth Measure Following Extremely Preterm Birth | At 36 weeks post-menstrual age | This is measured as the weight Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average weight, and negative scores denote less than average weight. |
| Follow-up Weight Growth Measure Following Extremely Preterm Birth | At 22-26 months corrected age | This is measured as the weight Z-score at 22-26 months corrected age. The Z-score is determined using the WHO weight-for-age chart, and is derived from a standardized normal distribution, where 0 designates average weight-for-age, and negative scores denote less than average weight-for-age. |
| Length Growth Measure Following Extremely Preterm Birth | At 36 weeks post-menstrual age | This is measured as the length Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average length, and negative scores denote less than average length. |
| Follow-up Length Growth Measure Following Extremely Preterm Birth | At 22-26 months corrected age | This is measured as the length Z-score at 22-26 months corrected age. The Z-score is determined using the WHO length-for-age chart, and is derived from a standardized normal distribution, where 0 designates average length-for-age, and negative scores denote less than average length-for-age. |
| Head Circumference Growth Measure Following Extremely Preterm Birth | At 36 weeks post-menstrual age | This is measured as the head circumference Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average head circumference, and negative scores denote less than average head circumference. |
| Follow-up Head Circumference Growth Measure Following Extremely Preterm Birth | At 22-26 months corrected age | This is measured as the head circumference Z-score at 22-26 months corrected age. The Z-score is determined using the WHO head circumference-for-age chart, and is derived from a standardized normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age. |
| Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | At 40 weeks post menstrual age | BPD grade at 40 weeks postmenstrual age. BPD grades are defined as: 1. No support/room air; 2. Nasal cannula (NC) O2 less than or equal to 2L; 3. NC O2 greater than 2L or CPAP/NIPPV; 4. Invasive PPV |
| Days of Mechanical Ventilation up to Status | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of days on mechanical ventilation (using high frequency ventilator or conventional ventilator) up to status |
| Number of Participants With Successful Extubation | From day of randomization to day 14 post randomization | Successful extubation during the intervention period, defined as remaining extubated for greater than or equal to 1 week, including greater than or equal to 3 days after the last dose of study medication. An extubation attempt was required after 72 hours of study drug and 24 hours after meeting the following: FiO2 less than 0.40 to maintain a saturation of greater than or equal to 88 percent, mean airway pressure less than 8 cm H2O, and hemodynamically stable in the opinion of the clinical team. |
| Duration of Invasive Positive Pressure Ventilation (PPV) After Postnatal Day 14 | From postnatal day 15 to 36 weeks post menstrual age or Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of days on invasive PPV after postnatal day 14 |
| Duration of Non-invasive Positive Pressure Ventilation (PPV) (Nasal IPPV/CPAP) After Postnatal Day 14 | From postnatal day 15 to 36 weeks post menstrual age or Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of days of non-invasive PPV after postnatal day 14 |
| Number of Participants Who Received Inhaled Glucocorticoids During Study Period | From randomization to day 14 post randomization | Number of infants who received Inhaled glucocorticoids during the study intervention period |
| Number of Participants Who Received Other Systemic Glucocorticoids During Study Period | From randomization to day 14 post randomization | Number of infants who received other systemic glucocorticoids during the study intervention period |
| Number of Days Dexamethasone Given Before 36 Weeks PMA | From birth to 36 weeks postmenstrual age | Number of days infant received dexamethasone anytime before 36 weeks postmenstrual age. |
| Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants with a Patent Ductus Arteriosus (PDA) that was treated with medicine or surgery |
| Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC) | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants diagnosed with Necrotizing Enterocolitis (NEC) |
| Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants diagnosed with ROP stage 3 or worse in either eye. ROP stage 3 or worse is determined based on the extent of extraretinal fibrovascular proliferation. Higher stages of ROP indicate a worse outcome; the stages range from 1 for mild disease, to 5 for severe disease. |
| Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP) | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants receiving therapy for Retinopathy of prematurity (ROP) |
| Number of Participants With Severe Intraventricular Hemorrhage (IVH) | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants with severe IVH, grade 3 or 4. Severity of IVH is hierarchical. Grade 3 occurs when the ventricular size is enlarged and blood/echodensity is in the ventricle. Grade 4 occurs when blood/echodensity is in the parenchyma. |
| Number of Participants With Periventricular Leukomalacia | From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Number of infants with Periventricular leukomalacia |
| Number of Participants With Neurodevelopmental Impairment (NDI) | At 22-26 months corrected age | Number of infants with NDI. NDI is defined as defined as any of: Bayley Scales of Infant and Toddler Development-III (Bayley-III) cognitive composite score less than 85 (standardized mean 100, SD 15, range 55-145) or motor composite score less than 85 (standardized mean 100, range 45-155) (lower scores indicating greater impairment), Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment), severe vision impairment in both eyes (consistent with refraction less than 20-200), or bilateral hearing impairment with or without amplification (by report). |
| Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85 | At 22-26 months corrected age | Number of infants with a BSID-III cognitive composite score less than 85. (standardized mean 100, SD 15, range 55-145). Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100. |
| Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70 | At 22-26 months corrected age | Number of infants with a BSID-III cognitive composite score less than 70. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100. |
| Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85 | At 22-26 months corrected age | Number of infants with a BSID-III motor composite score less than 85. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100. |
| Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70 | At 22-26 months corrected age | Number of infants with a BSID-III motor composite score less than 70. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100. |
| Number of Participants With Any Cerebral Palsy | At 22-26 months corrected age | Number of infants with cerebral palsy. Cerebral Palsy was diagnosed when there were definite abnormalities observed in the neuromotor exam, and functional challenges as classified by GMFCS level, and classified as moderate if GMFCS level was II or III and severe if level IV or V (40). |
| Duration of Oxygen Supplementation Among Survivors to 36 Weeks | From birth to 36 weeks postmenstrual age | Number of days of oxygen supplementation from birth to 36 weeks post menstrual age |
| Total Deaths Before Discharge | From day of randomization to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Infant died before discharge home. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydrocortisone Hydrocortisone sodium succinate administered intravenously or orally if no intravenous line was available, tapered over 10 days. | 398 |
| Placebo Saline placebo administered intravenously or orally if no intravenous line was available. | 402 |
| Total | 800 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incomplete Follow-up or No Study Data | 12 | 15 |
| Overall Study | Lost to Follow-up | 22 | 23 |
Baseline characteristics
| Characteristic | Total | Placebo | Hydrocortisone |
|---|---|---|---|
| Age, Continuous | 24.9 weeks STANDARD_DEVIATION 2 | 24.9 weeks STANDARD_DEVIATION 2 | 24.9 weeks STANDARD_DEVIATION 2 |
| Infant Body Weight | 715.4 grams STANDARD_DEVIATION 167.3 | 720.4 grams STANDARD_DEVIATION 171.8 | 710.3 grams STANDARD_DEVIATION 162.7 |
| Maternal Education College degree/more | 135 Participants | 69 Participants | 66 Participants |
| Maternal Education High school degree | 209 Participants | 108 Participants | 101 Participants |
| Maternal Education Less than High school degree | 127 Participants | 59 Participants | 68 Participants |
| Maternal Education Partial college | 163 Participants | 85 Participants | 78 Participants |
| Maternal Education Unknown | 166 Participants | 81 Participants | 85 Participants |
| Race/Ethnicity, Customized Black | 307 Participants | 168 Participants | 139 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 126 Participants | 60 Participants | 66 Participants |
| Race/Ethnicity, Customized Missing | 21 Participants | 11 Participants | 10 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 663 Participants | 337 Participants | 326 Participants |
| Race/Ethnicity, Customized Other | 35 Participants | 17 Participants | 18 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 11 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 437 Participants | 206 Participants | 231 Participants |
| Sex: Female, Male Female | 379 Participants | 167 Participants | 212 Participants |
| Sex: Female, Male Male | 421 Participants | 235 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 43 / 398 | 46 / 402 |
| other Total, other adverse events | 106 / 398 | 95 / 402 |
| serious Total, serious adverse events | 84 / 398 | 95 / 402 |
Outcome results
Primary
Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI)
Survival without moderate or severe neurodevelopmental impairment (NDI) at 22-26 months corrected age. NDI is defined as defined as any of: Bayley Scales of Infant and Toddler Development-III (Bayley-III) cognitive composite score less than 85 (standardized mean 100, SD 15, range 55-145) or motor composite score less than 85 (standardized mean 100, range 45-155) (lower scores indicating greater impairment), Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment), severe vision impairment in both eyes (consistent with refraction from less than 20 to 200), or bilateral hearing impairment with or without amplification (by report).
Time frame: From day of randomization to 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI) | Moderate/severe NDI or death | 226 Participants |
| Hydrocortisone | Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI) | Survival without moderate/severe neurodevelopmental impairment (NDI) | 132 Participants |
| Placebo | Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI) | Moderate/severe NDI or death | 226 Participants |
| Placebo | Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI) | Survival without moderate/severe neurodevelopmental impairment (NDI) | 134 Participants |
Primary
Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD)
Survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. Moderate or severe physiologic BPD is defined as a requirement for supplemental oxygen and/or positive airway pressure to maintain oxygen saturation greater than 90 percent. A room air challenge was performed for infants estimated to be receiving less than 0.30 FiO2 by nasal cannula.
Time frame: From day of randomization to 36 weeks post menstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD) | Moderate/severe BPD or death | 332 Participants |
| Hydrocortisone | Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD) | Survival without moderate/severe physiologic bronchopulmonary dysplasia (BPD) | 66 Participants |
| Placebo | Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD) | Moderate/severe BPD or death | 349 Participants |
| Placebo | Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD) | Survival without moderate/severe physiologic bronchopulmonary dysplasia (BPD) | 53 Participants |
Secondary
Days of Mechanical Ventilation to 36 Weeks Postmenstrual Age (PMA)
Number of days on mechanical ventilation (using high frequency ventilator or conventional ventilator)
Time frame: From birth to 36 weeks postmenstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Days of Mechanical Ventilation to 36 Weeks Postmenstrual Age (PMA) | 37 Days |
| Placebo | Days of Mechanical Ventilation to 36 Weeks Postmenstrual Age (PMA) | 40 Days |
Secondary
Days of Mechanical Ventilation up to Status
Number of days on mechanical ventilation (using high frequency ventilator or conventional ventilator) up to status
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data who survived up to hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Days of Mechanical Ventilation up to Status | 37 Days |
| Placebo | Days of Mechanical Ventilation up to Status | 41 Days |
Secondary
Duration of Invasive Positive Pressure Ventilation (PPV) After Postnatal Day 14
Number of days on invasive PPV after postnatal day 14
Time frame: From postnatal day 15 to 36 weeks post menstrual age or Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data who were extubated prior to hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Invasive Positive Pressure Ventilation (PPV) After Postnatal Day 14 | 29 Days |
| Placebo | Duration of Invasive Positive Pressure Ventilation (PPV) After Postnatal Day 14 | 27 Days |
Secondary
Duration of Non-invasive Positive Pressure Ventilation (PPV) (Nasal IPPV/CPAP) After Postnatal Day 14
Number of days of non-invasive PPV after postnatal day 14
Time frame: From postnatal day 15 to 36 weeks post menstrual age or Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data who were extubated prior to hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Non-invasive Positive Pressure Ventilation (PPV) (Nasal IPPV/CPAP) After Postnatal Day 14 | 13 Days |
| Placebo | Duration of Non-invasive Positive Pressure Ventilation (PPV) (Nasal IPPV/CPAP) After Postnatal Day 14 | 13 Days |
Secondary
Duration of Oxygen Supplementation Among Survivors to 36 Weeks
Number of days of oxygen supplementation from birth to 36 weeks post menstrual age
Time frame: From birth to 36 weeks postmenstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Oxygen Supplementation Among Survivors to 36 Weeks | 74 Days |
| Placebo | Duration of Oxygen Supplementation Among Survivors to 36 Weeks | 73 Days |
Secondary
Duration of Oxygen Supplementation up to Status
Number of days of oxygen supplementation from birth to discharge home
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data who survived up to hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Oxygen Supplementation up to Status | 104.5 Days |
| Placebo | Duration of Oxygen Supplementation up to Status | 104 Days |
Secondary
Follow-up Head Circumference Growth Measure Following Extremely Preterm Birth
This is measured as the head circumference Z-score at 22-26 months corrected age. The Z-score is determined using the WHO head circumference-for-age chart, and is derived from a standardized normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data between 18 and 30 months at follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Follow-up Head Circumference Growth Measure Following Extremely Preterm Birth | -0.45 Z-score | Standard Deviation 1.41 |
| Placebo | Follow-up Head Circumference Growth Measure Following Extremely Preterm Birth | -0.35 Z-score | Standard Deviation 1.42 |
Secondary
Follow-up Length Growth Measure Following Extremely Preterm Birth
This is measured as the length Z-score at 22-26 months corrected age. The Z-score is determined using the WHO length-for-age chart, and is derived from a standardized normal distribution, where 0 designates average length-for-age, and negative scores denote less than average length-for-age.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data between 18 and 30 months at follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Follow-up Length Growth Measure Following Extremely Preterm Birth | -0.93 Z-score | Standard Deviation 1.17 |
| Placebo | Follow-up Length Growth Measure Following Extremely Preterm Birth | -0.94 Z-score | Standard Deviation 1.22 |
Secondary
Follow-up Weight Growth Measure Following Extremely Preterm Birth
This is measured as the weight Z-score at 22-26 months corrected age. The Z-score is determined using the WHO weight-for-age chart, and is derived from a standardized normal distribution, where 0 designates average weight-for-age, and negative scores denote less than average weight-for-age.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data between 18 and 30 months at follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Follow-up Weight Growth Measure Following Extremely Preterm Birth | -0.51 Z-score | Standard Deviation 1.04 |
| Placebo | Follow-up Weight Growth Measure Following Extremely Preterm Birth | -0.44 Z-score | Standard Deviation 1.15 |
Secondary
Head Circumference Growth Measure Following Extremely Preterm Birth
This is measured as the head circumference Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average head circumference, and negative scores denote less than average head circumference.
Time frame: At 36 weeks post-menstrual age
Population: The analysis population includes all randomized infants with available data between 35 and 37 weeks at discharge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Head Circumference Growth Measure Following Extremely Preterm Birth | -1.68 Z-score | Standard Deviation 1.34 |
| Placebo | Head Circumference Growth Measure Following Extremely Preterm Birth | -1.74 Z-score | Standard Deviation 1.17 |
Secondary
Length Growth Measure Following Extremely Preterm Birth
This is measured as the length Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average length, and negative scores denote less than average length.
Time frame: At 36 weeks post-menstrual age
Population: The analysis population includes all randomized infants with available data between 35 and 37 weeks at discharge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Length Growth Measure Following Extremely Preterm Birth | -2.33 Z-score | Standard Deviation 1.16 |
| Placebo | Length Growth Measure Following Extremely Preterm Birth | -2.21 Z-score | Standard Deviation 1.14 |
Secondary
Length of Hospital Stay in Days Among Survivors to Discharge
Number of days infant stayed in hospitals, among those who survived to discharge
Time frame: From birth up to one year
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Length of Hospital Stay in Days Among Survivors to Discharge | 127.5 Days |
| Placebo | Length of Hospital Stay in Days Among Survivors to Discharge | 125.5 Days |
Secondary
Number of Days Dexamethasone Given Before 36 Weeks PMA
Number of days infant received dexamethasone anytime before 36 weeks postmenstrual age.
Time frame: From birth to 36 weeks postmenstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Number of Days Dexamethasone Given Before 36 Weeks PMA | 10 Days |
| Placebo | Number of Days Dexamethasone Given Before 36 Weeks PMA | 10 Days |
Secondary
Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC)
Number of infants diagnosed with Necrotizing Enterocolitis (NEC)
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC) | Diagnosed with NEC | 33 Participants |
| Hydrocortisone | Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC) | Not diagnosed with NEC | 365 Participants |
| Placebo | Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC) | Diagnosed with NEC | 46 Participants |
| Placebo | Number of Participants Diagnosed With Necrotizing Enterocolitis (NEC) | Not diagnosed with NEC | 356 Participants |
Secondary
Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP)
Number of infants receiving therapy for Retinopathy of prematurity (ROP)
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP) | Did not receive therapy for ROP | 311 Participants |
| Hydrocortisone | Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP) | Received therapy for ROP | 68 Participants |
| Placebo | Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP) | Did not receive therapy for ROP | 293 Participants |
| Placebo | Number of Participants Receiving Therapy for Retinopathy of Prematurity (ROP) | Received therapy for ROP | 83 Participants |
Secondary
Number of Participants Who Received Inhaled Glucocorticoids During Study Period
Number of infants who received Inhaled glucocorticoids during the study intervention period
Time frame: From randomization to day 14 post randomization
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants Who Received Inhaled Glucocorticoids During Study Period | Did not receive inhaled glucocorticoids during study period | 345 Participants |
| Hydrocortisone | Number of Participants Who Received Inhaled Glucocorticoids During Study Period | Received inhaled glucocorticoids during study period | 51 Participants |
| Placebo | Number of Participants Who Received Inhaled Glucocorticoids During Study Period | Did not receive inhaled glucocorticoids during study period | 355 Participants |
| Placebo | Number of Participants Who Received Inhaled Glucocorticoids During Study Period | Received inhaled glucocorticoids during study period | 44 Participants |
Secondary
Number of Participants Who Received Other Systemic Glucocorticoids During Study Period
Number of infants who received other systemic glucocorticoids during the study intervention period
Time frame: From randomization to day 14 post randomization
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants Who Received Other Systemic Glucocorticoids During Study Period | Did not receive other systemic glucocorticoids during study period | 342 Participants |
| Hydrocortisone | Number of Participants Who Received Other Systemic Glucocorticoids During Study Period | Received other systemic glucocorticoids during study period | 54 Participants |
| Placebo | Number of Participants Who Received Other Systemic Glucocorticoids During Study Period | Did not receive other systemic glucocorticoids during study period | 334 Participants |
| Placebo | Number of Participants Who Received Other Systemic Glucocorticoids During Study Period | Received other systemic glucocorticoids during study period | 65 Participants |
Secondary
Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70
Number of infants with a BSID-III cognitive composite score less than 70. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70 | Composite cognitive score greater or equal to 70 | 259 Participants |
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70 | Composite cognitive score less than 70 | 59 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70 | Composite cognitive score greater or equal to 70 | 269 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 70 | Composite cognitive score less than 70 | 49 Participants |
Secondary
Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85
Number of infants with a BSID-III cognitive composite score less than 85. (standardized mean 100, SD 15, range 55-145). Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85 | Composite cognitive score greater or equal to 85 | 168 Participants |
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85 | Composite cognitive score less than 85 | 150 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85 | Composite cognitive score greater or equal to 85 | 176 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Cognitive Composite Score Less Than 85 | Composite cognitive score less than 85 | 142 Participants |
Secondary
Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70
Number of infants with a BSID-III motor composite score less than 70. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70 | Composite motor score greater or equal to 70 | 241 Participants |
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70 | Composite motor score less than 70 | 69 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70 | Composite motor score greater or equal to 70 | 246 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 70 | Composite motor score less than 70 | 64 Participants |
Secondary
Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85
Number of infants with a BSID-III motor composite score less than 85. (standardized mean 100, SD 15, range 55-145). Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85 | Composite motor score greater or equal to 85 | 164 Participants |
| Hydrocortisone | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85 | Composite motor score less than 85 | 146 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85 | Composite motor score greater or equal to 85 | 158 Participants |
| Placebo | Number of Participants With a Bayley Scales of Infant Development (BSID) Motor Composite Score Less Than 85 | Composite motor score less than 85 | 152 Participants |
Secondary
Number of Participants With Any Cerebral Palsy
Number of infants with cerebral palsy. Cerebral Palsy was diagnosed when there were definite abnormalities observed in the neuromotor exam, and functional challenges as classified by GMFCS level, and classified as moderate if GMFCS level was II or III and severe if level IV or V (40).
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Any Cerebral Palsy | Any cerebral palsy | 84 Participants |
| Hydrocortisone | Number of Participants With Any Cerebral Palsy | No cerebral palsy | 246 Participants |
| Placebo | Number of Participants With Any Cerebral Palsy | Any cerebral palsy | 71 Participants |
| Placebo | Number of Participants With Any Cerebral Palsy | No cerebral palsy | 259 Participants |
Secondary
Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age
BPD grade at 40 weeks postmenstrual age. BPD grades are defined as: 1. No support/room air; 2. Nasal cannula (NC) O2 less than or equal to 2L; 3. NC O2 greater than 2L or CPAP/NIPPV; 4. Invasive PPV
Time frame: At 40 weeks post menstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | Invasive PPV | 46 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | NC O2 greater than 2L or CPAP/NIPPV | 73 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | Nasal cannula O2 less than or equal to 2L | 124 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | No support, room air | 36 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | No support, room air | 52 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | Invasive PPV | 38 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | Nasal cannula O2 less than or equal to 2L | 129 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade 40 Weeks Postmenstrual Age | NC O2 greater than 2L or CPAP/NIPPV | 65 Participants |
Secondary
Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age
BPD grade at 36 weeks postmenstrual age. BPD grades are defined as: 1. No support/room air; 2. Nasal cannula (NC) O2 less than or equal to 2L; 3. NC O2 greater than 2L or CPAP/NIPPV; 4. Invasive PPV
Time frame: At 36 weeks postmenstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | Invasive PPV | 63 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | NC O2 greater than 2L or CPAP/NIPPV | 152 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | Nasal cannula O2 less than or equal to 2L | 120 Participants |
| Hydrocortisone | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | No support, room air | 40 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | No support, room air | 33 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | Invasive PPV | 51 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | Nasal cannula O2 less than or equal to 2L | 124 Participants |
| Placebo | Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age | NC O2 greater than 2L or CPAP/NIPPV | 159 Participants |
Secondary
Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA)
Infant received dexamethasone anytime before 36 weeks postmenstrual age.
Time frame: From birth to 36 weeks postmenstrual age
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA) | Dexamethasone given before 36 weeks PMA | 150 Participants |
| Hydrocortisone | Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA) | Dexamethasone not given before 36 weeks PMA | 229 Participants |
| Placebo | Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA) | Dexamethasone given before 36 weeks PMA | 157 Participants |
| Placebo | Number of Participants With Dexamethasone Given Before 36 Weeks Postmenstrual Age (PMA) | Dexamethasone not given before 36 weeks PMA | 220 Participants |
Secondary
Number of Participants With Gross Motor Function Greater Than or Equal to Level 2
Number of infants with Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment)
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data who survived up to the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Gross Motor Function Greater Than or Equal to Level 2 | Gross motor function less than II | 283 Participants |
| Hydrocortisone | Number of Participants With Gross Motor Function Greater Than or Equal to Level 2 | Gross motor function level II or greater | 48 Participants |
| Placebo | Number of Participants With Gross Motor Function Greater Than or Equal to Level 2 | Gross motor function less than II | 288 Participants |
| Placebo | Number of Participants With Gross Motor Function Greater Than or Equal to Level 2 | Gross motor function level II or greater | 41 Participants |
Secondary
Number of Participants With Moderate-severe Cerebral Palsy
Number of infants with moderate or severe grade of cerebral palsy. Cerebral Palsy was diagnosed when there were definite abnormalities observed in the neuromotor exam, and functional challenges as classified by GMFCS level, and classified as moderate if GMFCS level was II or III and severe if level IV or V (40).
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data who survived up to the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Moderate-severe Cerebral Palsy | Moderate or severe cerebral palsy | 41 Participants |
| Hydrocortisone | Number of Participants With Moderate-severe Cerebral Palsy | Not moderate or severe cerebral palsy | 289 Participants |
| Placebo | Number of Participants With Moderate-severe Cerebral Palsy | Moderate or severe cerebral palsy | 33 Participants |
| Placebo | Number of Participants With Moderate-severe Cerebral Palsy | Not moderate or severe cerebral palsy | 297 Participants |
Secondary
Number of Participants With Neurodevelopmental Impairment (NDI)
Number of infants with NDI. NDI is defined as defined as any of: Bayley Scales of Infant and Toddler Development-III (Bayley-III) cognitive composite score less than 85 (standardized mean 100, SD 15, range 55-145) or motor composite score less than 85 (standardized mean 100, range 45-155) (lower scores indicating greater impairment), Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment), severe vision impairment in both eyes (consistent with refraction less than 20-200), or bilateral hearing impairment with or without amplification (by report).
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data at the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Neurodevelopmental Impairment (NDI) | Neurodevelopmental impairment | 189 Participants |
| Hydrocortisone | Number of Participants With Neurodevelopmental Impairment (NDI) | No neurodevelopmental impairment | 132 Participants |
| Placebo | Number of Participants With Neurodevelopmental Impairment (NDI) | Neurodevelopmental impairment | 185 Participants |
| Placebo | Number of Participants With Neurodevelopmental Impairment (NDI) | No neurodevelopmental impairment | 134 Participants |
Secondary
Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI
Severity of neurodevelopmental impairment, defined as one or more of: Bayley Scales of Infant Development-III (Bayley-III) cognitive score \<85 (standardized mean 100, SD 15, range 55-145), Bayley-III motor score \<85 (standardized mean 100, range 45-155), Gross Motor Function Classification System (GMFCS) level ≥2, severe vision impairment in both eyes (consistent with refraction \<20-200), or bilateral hearing impairment with or without amplification (by report). Bayley-III = Bayley Scales of Infant Development III (Cognitive score standardized mean 100, SD 15, range 55-145 motor score standardized mean 100, range 45-155; higher score indicates better performance (20))
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data who survived up to the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Moderate | 98 Participants |
| Hydrocortisone | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Normal/mild | 132 Participants |
| Hydrocortisone | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Severe/profound | 85 Participants |
| Placebo | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Moderate | 98 Participants |
| Placebo | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Normal/mild | 134 Participants |
| Placebo | Number of Participants With Normal/Mild, Moderate or Severe/Profound NDI | Severe/profound | 82 Participants |
Secondary
Number of Participants With no/Some Functional Vision
Number of infants with severe vision impairment in both eyes (consistent with refraction less than 20-200)
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data who survived up to the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With no/Some Functional Vision | Not severe vision impairment | 325 Participants |
| Hydrocortisone | Number of Participants With no/Some Functional Vision | Severe vision impairment | 5 Participants |
| Placebo | Number of Participants With no/Some Functional Vision | Not severe vision impairment | 321 Participants |
| Placebo | Number of Participants With no/Some Functional Vision | Severe vision impairment | 9 Participants |
Secondary
Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery
Number of infants with a Patent Ductus Arteriosus (PDA) that was treated with medicine or surgery
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery | Not PDA treated with medication or surgery | 206 Participants |
| Hydrocortisone | Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery | PDA treated with medication or surgery | 192 Participants |
| Placebo | Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery | Not PDA treated with medication or surgery | 209 Participants |
| Placebo | Number of Participants With Patent Ductus Arteriosus (PDA) Treated With Medication or Surgery | PDA treated with medication or surgery | 193 Participants |
Secondary
Number of Participants With Periventricular Leukomalacia
Number of infants with Periventricular leukomalacia
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Periventricular Leukomalacia | No periventricular leukomalacia | 376 Participants |
| Hydrocortisone | Number of Participants With Periventricular Leukomalacia | Periventricular leukomalacia | 22 Participants |
| Placebo | Number of Participants With Periventricular Leukomalacia | No periventricular leukomalacia | 378 Participants |
| Placebo | Number of Participants With Periventricular Leukomalacia | Periventricular leukomalacia | 24 Participants |
Secondary
Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse
Number of infants diagnosed with ROP stage 3 or worse in either eye. ROP stage 3 or worse is determined based on the extent of extraretinal fibrovascular proliferation. Higher stages of ROP indicate a worse outcome; the stages range from 1 for mild disease, to 5 for severe disease.
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse | Diagnosed with ROP stage 3 or worse | 105 Participants |
| Hydrocortisone | Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse | Not diagnosed with ROP stage 3 or worse | 277 Participants |
| Placebo | Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse | Diagnosed with ROP stage 3 or worse | 116 Participants |
| Placebo | Number of Participants With Retinopathy of Prematurity (ROP) Stage 3 or Worse | Not diagnosed with ROP stage 3 or worse | 260 Participants |
Secondary
Number of Participants With Severe Hearing Impairment (by Report)
Number of infants with bilateral hearing impairment with or without amplification (by report)
Time frame: At 22-26 months corrected age
Population: The analysis population includes all randomized infants with available data who survived up to the two-year followup.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Severe Hearing Impairment (by Report) | Not severe hearing impairment | 319 Participants |
| Hydrocortisone | Number of Participants With Severe Hearing Impairment (by Report) | Severe hearing impairment | 9 Participants |
| Placebo | Number of Participants With Severe Hearing Impairment (by Report) | Not severe hearing impairment | 313 Participants |
| Placebo | Number of Participants With Severe Hearing Impairment (by Report) | Severe hearing impairment | 14 Participants |
Secondary
Number of Participants With Severe Intraventricular Hemorrhage (IVH)
Number of infants with severe IVH, grade 3 or 4. Severity of IVH is hierarchical. Grade 3 occurs when the ventricular size is enlarged and blood/echodensity is in the ventricle. Grade 4 occurs when blood/echodensity is in the parenchyma.
Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Severe Intraventricular Hemorrhage (IVH) | Not severe IVH, grade 3 or 4 | 316 Participants |
| Hydrocortisone | Number of Participants With Severe Intraventricular Hemorrhage (IVH) | Severe IVH, grade 3 or 4 | 81 Participants |
| Placebo | Number of Participants With Severe Intraventricular Hemorrhage (IVH) | Not severe IVH, grade 3 or 4 | 331 Participants |
| Placebo | Number of Participants With Severe Intraventricular Hemorrhage (IVH) | Severe IVH, grade 3 or 4 | 71 Participants |
Secondary
Number of Participants With Successful Extubation
Successful extubation during the intervention period, defined as remaining extubated for greater than or equal to 1 week, including greater than or equal to 3 days after the last dose of study medication. An extubation attempt was required after 72 hours of study drug and 24 hours after meeting the following: FiO2 less than 0.40 to maintain a saturation of greater than or equal to 88 percent, mean airway pressure less than 8 cm H2O, and hemodynamically stable in the opinion of the clinical team.
Time frame: From day of randomization to day 14 post randomization
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Successful Extubation | Successful extubation | 178 Participants |
| Hydrocortisone | Number of Participants With Successful Extubation | Unsuccessful or no extubation | 220 Participants |
| Placebo | Number of Participants With Successful Extubation | Successful extubation | 135 Participants |
| Placebo | Number of Participants With Successful Extubation | Unsuccessful or no extubation | 267 Participants |
Secondary
Total Deaths Before Discharge
Infant died before discharge home.
Time frame: From day of randomization to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: The analysis population includes all randomized infants with available data at hospital discharge.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Total Deaths Before Discharge | Death before discharge | 35 Participants |
| Hydrocortisone | Total Deaths Before Discharge | Survival to discharge | 363 Participants |
| Placebo | Total Deaths Before Discharge | Survival to discharge | 362 Participants |
| Placebo | Total Deaths Before Discharge | Death before discharge | 40 Participants |
Secondary
Weight Growth Measure Following Extremely Preterm Birth
This is measured as the weight Z-score at 36 weeks postmenstrual age. The Z-score is derived using Fenton growth curves, and follows a standardized normal distribution with a mean 0. A z-score of 0 designates average weight, and negative scores denote less than average weight.
Time frame: At 36 weeks post-menstrual age
Population: The analysis population includes all randomized infants with available data between 35 and 37 weeks at discharge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Weight Growth Measure Following Extremely Preterm Birth | -1.68 Z-score | Standard Deviation 1.01 |
| Placebo | Weight Growth Measure Following Extremely Preterm Birth | -1.65 Z-score | Standard Deviation 0.98 |