Cardiovascular Insufficiency, Infant, Newborn, Diseases
Conditions
Keywords
NICHD Neonatal Research Network, Mechanical ventilation, Intubation, Neurodevelopmental impairment
Brief summary
This trial will evaluate the effects of a 7-day course of hydrocortisone therapy on short-term morbidity, cardiovascular function, long-term neurodevelopment, and mortality in critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
Detailed description
Cardiovascular insufficiency is common and potentially life-threatening in critically ill term and late preterm newborns admitted to the newborn intensive care unit (NICU) in the first few days of age. This study proposes to conduct a multicenter, randomized, masked, placebo-controlled trial within the Neonatal Research Network (NRN). This trial will evaluate the effects of a 7-day course of hydrocortisone therapy on short-term morbidity, cardiovascular function, long-term neurodevelopment, and mortality in critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
Interventions
DRUGHydrocortisone
• 7 day course of hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line). 1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose
DRUGPlacebo
7 days of intravenous or intramuscular placebo (normal saline in equal volume) 1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose
Sponsors
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
34 Weeks to No maximum
Healthy volunteers
No
Inclusion criteria
* Gestational age greater than or equal to 34 weeks at birth * Admitted to the center NICU by 48 hours of age * Intubated and mechanically ventilated for a minimum of 2 hours before 72 hours postnatal age
Exclusion criteria
* Receiving ECMO * Intubated for the sole purpose of anticipated surgery or airway anomalies * Treatment will be limited based on poor prognosis * Receiving dexamethasone or hydrocortisone * Receiving ibuprofen or indomethacin * Congenital heart disease * Hypotension thought to result from specific, immediately remediable factors including placental hemorrhage, acute hemorrhage or tension pneumothorax * Pituitary hypoplasia or congenital adrenal hyperplasia * Any chromosomal disorder * Hypertension in the absence of inotrope therapy as defined by mean arterial blood pressure \> 95th percentile * Initiation of whole body cooling for moderate or severe neonatal encephalopathy * Brain disorders or any other known structural abnormality * Major anomalies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death | Birth to 22-26 months corrected gestational age | This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No. |
| Number of Participants With Neurodevelopmental Impairment | Birth to 22-26 months corrected gestational age | This is measured as Yes if an any hearing impairment or visual impairment is noted, if non-normal gross motor function level is noted, any seizures have been noted, or if the cognitive, language, or motor scores of the Bayley III score are more than 1 standard deviation below the average; Otherwise, No. |
| Number of Participants With Death or Neurodevelopmental Impairment | Birth to 22-26 months corrected gestational age | A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected gestational age. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Oxygen Requirement | Birth to 60 days of life | This is measured as the number of days between birth and 60 days of life that an infant was on oxygen in the hospital. |
| Number of Participants With Need for Home Oxygen | Birth to 60 days of life | This is measured as Yes if an infant was discharged to home while on oxygen between birth and 60 days of life; Otherwise, No. |
| Hospital Length of Stay | Birth to 60 days of life | This is measured as the number of days between birth and 60 days of life that an infant was in the hospital. Infants who died or transferred to another care facility were not included. |
| Number of Participants With Renal Insufficiency | Birth to 60 days of life | This is measured as Yes if an infant had renal insufficieny between birth and 60 days of life; Otherwise, No. Renal insufficiency is defined as creatinine less than 2 during 7 days after first treatment |
| Number of Participants With Necrotizing Enterocolitis | Birth to 60 days of life | This is measured as Yes if an infant necrotizing enterocolitis (NEC) between birth and 60 days of life; Otherwise, No. NEC could be proven with or without surgery |
| Number of Participants With Need for ECMO Therapy | Birth to 60 days of life | This is measured as Yes if an infant received ECMO treatment anytime between birth and 60 days of life; Otherwise, No. Extracorporeal membrane oxygenation (ECMO) is a treatment that uses a pump to circulate blood through an artificial lung back into the bloodstream of a very ill baby. |
| Duration of Mechanical Ventilation | Birth to 60 days of life | This is measured as the number of days between birth and 60 days of life of mechanical ventialtion of laryngeal intubation. |
| Inotrope Duration | 24 hours prior to study drug administration through 3 days post study drug administration. | This is calculated as the number of days on inotropes starting 24 hours prior to initiation of study drug, during the 7-day study drug administration period, and for 3 days after the study drug. |
| Maximum Inotrope Dose | From start of study drug administration (7 days) through 3 days post study drug administration. | This is calculated as the maximum dose of all inotropes in the 10 days following the initiation of study drug administration. For the purposes of this calculation, dopamine and dobutamine doses were considered equivalent and 0.01 mcg/kg/min of epinephrine was equal to 5 mcg/kg/min of dopamine. |
| Oxygenation Index | Birth to 60 days of life | This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure divided by partial pressure of oxygen in arterial blood (PaO2), during study drug administration. A lower oxygenation index is better. |
| Respiratory Severity | Birth to 60 days of life | This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure during study drug administration. Higher score means more severe. |
| Number of Participants With Fluid Boluses Given | Birth to 60 days of life | This is measured as Yes if an infant received fluid boluses anytime before or during study drug administration between birth and 60 days of life; Otherwise, No. |
| Number of Boluses Given | Birth to 60 days of life | The number of fluid boluses given per participant, if any, before or during study drug administration between birth and 60 days of life |
| Number of Participants With Inotrope Exposure | 24 hours prior to study drug administration through 3 days post study drug administration. | This is measured as Yes if an infant was receiving inotropes on the specific day after the initiation of study drug. |
| Days to Full Feeds | Birth to 60 days of life | The day of life at which full nipple feeds were reached between birth and 60 days of life. Full nipple feeds are defined as at least 120 mg/kg/day. |
| Number of Participants With Need for Gastronomy Tube | Birth to 60 days of life | This is measured as Yes if a gastronomy tube was placed anytime prior to final status between birth and 60 days of life; Otherwise, No |
Countries
United States
Participant flow
Recruitment details
Infants \< 48 hours of age and born at ≥ 34 weeks gestational age were screened for the study between June 2014 and July 2015 at the 16 NRN Clinical Centers. Those who were intubated and on mechanical ventilation for at least 2 hours within the first 72 hours were considered for the study.
Participants by arm
| Arm | Count |
|---|---|
| Hydrocortisone Hydrocortisone: 7 day course of hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line).
1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose | 6 |
| Placebo Saline placebo: 7 days of intravenous or intramuscular placebo (normal saline in equal volume)
1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Birth to 22-26 Mos. Corrected GA | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Hydrocortisone | Placebo |
|---|---|---|---|
| Age, Continuous | 38.4 weeks STANDARD_DEVIATION 2.2 | 37.5 weeks STANDARD_DEVIATION 2.2 | 39.4 weeks STANDARD_DEVIATION 1.8 |
| Apgar score less than 3 at 10 minutes No | 6 Participants | 3 Participants | 3 Participants |
| Apgar score less than 3 at 10 minutes Unknown | 6 Participants | 3 Participants | 3 Participants |
| Apgar score less than 3 at 10 minutes Yes | 0 Participants | 0 Participants | 0 Participants |
| Apgar score less than 3 at 1 minute No | 6 Participants | 2 Participants | 4 Participants |
| Apgar score less than 3 at 1 minute Yes | 6 Participants | 4 Participants | 2 Participants |
| Apgar score less than 3 at 5 minutes No | 11 Participants | 5 Participants | 6 Participants |
| Apgar score less than 3 at 5 minutes Yes | 1 Participants | 1 Participants | 0 Participants |
| Bagging and Mask No | 3 Participants | 1 Participants | 2 Participants |
| Bagging and Mask Yes | 9 Participants | 5 Participants | 4 Participants |
| Birth weight | 3267.7 grams STANDARD_DEVIATION 600.3 | 3415 grams STANDARD_DEVIATION 669.3 | 3120.3 grams STANDARD_DEVIATION 541 |
| Chest Compression No | 10 Participants | 5 Participants | 5 Participants |
| Chest Compression Yes | 2 Participants | 1 Participants | 1 Participants |
| Final mode of delivery Cesarean section | 6 Participants | 3 Participants | 3 Participants |
| Final mode of delivery Unknown | 1 Participants | 0 Participants | 1 Participants |
| Final mode of delivery Vaginal vertex | 5 Participants | 3 Participants | 2 Participants |
| Head circumference | 34.5 cm STANDARD_DEVIATION 2.7 | 34.4 cm STANDARD_DEVIATION 2 | 34.5 cm STANDARD_DEVIATION 3.5 |
| Infant Outborn No | 6 Participants | 4 Participants | 2 Participants |
| Infant Outborn Yes | 6 Participants | 2 Participants | 4 Participants |
| Intubation No | 5 Participants | 4 Participants | 1 Participants |
| Intubation Yes | 7 Participants | 2 Participants | 5 Participants |
| Length | 49.9 cm STANDARD_DEVIATION 1.9 | 50.1 cm STANDARD_DEVIATION 2.3 | 49.8 cm STANDARD_DEVIATION 1.5 |
| Maternal Age, Continuous | 29.4 years STANDARD_DEVIATION 8.7 | 32.2 years STANDARD_DEVIATION 7.6 | 26.7 years STANDARD_DEVIATION 9.5 |
| Maternal antenatal steroids No | 12 Participants | 6 Participants | 6 Participants |
| Maternal antenatal steroids Yes | 0 Participants | 0 Participants | 0 Participants |
| Maternal documented chorioamnionitis No | 11 Participants | 5 Participants | 6 Participants |
| Maternal documented chorioamnionitis Yes | 1 Participants | 1 Participants | 0 Participants |
| Maternal gravida | 2 Number of pregnancies | 2.5 Number of pregnancies | 1 Number of pregnancies |
| Maternal marital Status Married | 2 Participants | 1 Participants | 1 Participants |
| Maternal marital Status Single | 10 Participants | 5 Participants | 5 Participants |
| Maternal multiple birth No | 12 Participants | 6 Participants | 6 Participants |
| Maternal multiple birth Yes | 0 Participants | 0 Participants | 0 Participants |
| Maternal parity | 2 Number of successful pregnancies | 2.5 Number of successful pregnancies | 1 Number of successful pregnancies |
| Maternal prenatal care No | 3 Participants | 2 Participants | 1 Participants |
| Maternal prenatal care Yes | 9 Participants | 4 Participants | 5 Participants |
| Maternal Race Black | 5 Participants | 3 Participants | 2 Participants |
| Maternal Race More than one race | 1 Participants | 0 Participants | 1 Participants |
| Maternal Race Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Maternal Race White | 5 Participants | 3 Participants | 2 Participants |
| Medications or volume expanders No | 8 Participants | 5 Participants | 3 Participants |
| Medications or volume expanders Yes | 4 Participants | 1 Participants | 3 Participants |
| Oxygen No | 0 Participants | 0 Participants | 0 Participants |
| Oxygen Yes | 12 Participants | 6 Participants | 6 Participants |
| Placental pathology performed No | 2 Participants | 1 Participants | 1 Participants |
| Placental pathology performed Unknown | 5 Participants | 3 Participants | 2 Participants |
| Placental pathology performed Yes | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 8 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Sex/Gender, Customized Female | 6 Participants | 2 Participants | 4 Participants |
| Sex/Gender, Customized Male | 6 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 |
Outcome results
Primary
Death
This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No.
Time frame: Birth to 22-26 months corrected gestational age
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Death | No | 6 Participants |
| Hydrocortisone | Death | Yes | 0 Participants |
| Placebo | Death | No | 6 Participants |
| Placebo | Death | Yes | 0 Participants |
Primary
Number of Participants With Death or Neurodevelopmental Impairment
A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected gestational age.
Time frame: Birth to 22-26 months corrected gestational age
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Death or Neurodevelopmental Impairment | Yes | 3 Participants |
| Hydrocortisone | Number of Participants With Death or Neurodevelopmental Impairment | No | 3 Participants |
| Placebo | Number of Participants With Death or Neurodevelopmental Impairment | Yes | 3 Participants |
| Placebo | Number of Participants With Death or Neurodevelopmental Impairment | No | 3 Participants |
Primary
Number of Participants With Neurodevelopmental Impairment
This is measured as Yes if an any hearing impairment or visual impairment is noted, if non-normal gross motor function level is noted, any seizures have been noted, or if the cognitive, language, or motor scores of the Bayley III score are more than 1 standard deviation below the average; Otherwise, No.
Time frame: Birth to 22-26 months corrected gestational age
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Neurodevelopmental Impairment | Yes | 3 Participants |
| Hydrocortisone | Number of Participants With Neurodevelopmental Impairment | No | 3 Participants |
| Placebo | Number of Participants With Neurodevelopmental Impairment | Yes | 3 Participants |
| Placebo | Number of Participants With Neurodevelopmental Impairment | No | 3 Participants |
Secondary
Days to Full Feeds
The day of life at which full nipple feeds were reached between birth and 60 days of life. Full nipple feeds are defined as at least 120 mg/kg/day.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age. Excludes 4 infants (Hydrocortisone: 1, Placebo: 3) without information on full feeds.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Days to Full Feeds | 16 Days |
| Placebo | Days to Full Feeds | 18 Days |
Secondary
Duration of Mechanical Ventilation
This is measured as the number of days between birth and 60 days of life of mechanical ventialtion of laryngeal intubation.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Mechanical Ventilation | 8 Days |
| Placebo | Duration of Mechanical Ventilation | 11 Days |
Secondary
Duration of Oxygen Requirement
This is measured as the number of days between birth and 60 days of life that an infant was on oxygen in the hospital.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Duration of Oxygen Requirement | 15.5 Days |
| Placebo | Duration of Oxygen Requirement | 18 Days |
Secondary
Hospital Length of Stay
This is measured as the number of days between birth and 60 days of life that an infant was in the hospital. Infants who died or transferred to another care facility were not included.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Hospital Length of Stay | 27 Days |
| Placebo | Hospital Length of Stay | 24 Days |
Secondary
Inotrope Duration
This is calculated as the number of days on inotropes starting 24 hours prior to initiation of study drug, during the 7-day study drug administration period, and for 3 days after the study drug.
Time frame: 24 hours prior to study drug administration through 3 days post study drug administration.
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydrocortisone | Inotrope Duration | 3 days |
| Placebo | Inotrope Duration | 3 days |
Secondary
Maximum Inotrope Dose
This is calculated as the maximum dose of all inotropes in the 10 days following the initiation of study drug administration. For the purposes of this calculation, dopamine and dobutamine doses were considered equivalent and 0.01 mcg/kg/min of epinephrine was equal to 5 mcg/kg/min of dopamine.
Time frame: From start of study drug administration (7 days) through 3 days post study drug administration.
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone | Maximum Inotrope Dose | 9.5 mcg/kg/min | Standard Deviation 2.9 |
| Placebo | Maximum Inotrope Dose | 14.7 mcg/kg/min | Standard Deviation 12.6 |
Secondary
Number of Boluses Given
The number of fluid boluses given per participant, if any, before or during study drug administration between birth and 60 days of life
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hydrocortisone | Number of Boluses Given | Before dose 1 | 3 Boluses |
| Hydrocortisone | Number of Boluses Given | Before dose 5 | 2 Boluses |
| Hydrocortisone | Number of Boluses Given | Before dose 9 | 2 Boluses |
| Hydrocortisone | Number of Boluses Given | Before dose 13 | 1 Boluses |
| Placebo | Number of Boluses Given | Before dose 15 | 1 Boluses |
| Placebo | Number of Boluses Given | Before dose 1 | 3 Boluses |
| Placebo | Number of Boluses Given | Before dose 9 | 1 Boluses |
| Placebo | Number of Boluses Given | Before dose 5 | 1 Boluses |
Secondary
Number of Participants With Fluid Boluses Given
This is measured as Yes if an infant received fluid boluses anytime before or during study drug administration between birth and 60 days of life; Otherwise, No.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 1 | No | 2 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 1 | Yes | 4 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 5 | No | 5 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 5 | Yes | 1 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 9 | No | 5 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 9 | Yes | 1 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 13 | No | 5 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 13 | Yes | 1 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 15 | No | 6 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 15 | Yes | 0 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 17 | No | 6 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 17 | Yes | 0 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 18 | No | 6 Participants |
| Hydrocortisone | Number of Participants With Fluid Boluses Given | Before dose 18 | Yes | 0 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 17 | No | 6 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 1 | No | 2 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 13 | Yes | 0 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 1 | Yes | 4 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 18 | No | 6 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 5 | No | 4 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 15 | No | 4 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 5 | Yes | 2 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 17 | Yes | 0 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 9 | No | 5 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 15 | Yes | 1 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 9 | Yes | 1 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 18 | Yes | 0 Participants |
| Placebo | Number of Participants With Fluid Boluses Given | Before dose 13 | No | 6 Participants |
Secondary
Number of Participants With Inotrope Exposure
This is measured as Yes if an infant was receiving inotropes on the specific day after the initiation of study drug.
Time frame: 24 hours prior to study drug administration through 3 days post study drug administration.
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 3 | Yes | 2 Participants |
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 3 | No | 4 Participants |
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 7 | No | 5 Participants |
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 5 | No | 5 Participants |
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 7 | Yes | 1 Participants |
| Hydrocortisone | Number of Participants With Inotrope Exposure | Day 5 | Yes | 1 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 7 | Yes | 1 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 3 | No | 4 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 3 | Yes | 2 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 5 | No | 4 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 5 | Yes | 2 Participants |
| Placebo | Number of Participants With Inotrope Exposure | Day 7 | No | 5 Participants |
Secondary
Number of Participants With Necrotizing Enterocolitis
This is measured as Yes if an infant necrotizing enterocolitis (NEC) between birth and 60 days of life; Otherwise, No. NEC could be proven with or without surgery
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Necrotizing Enterocolitis | No | 5 Participants |
| Hydrocortisone | Number of Participants With Necrotizing Enterocolitis | Yes | 1 Participants |
| Placebo | Number of Participants With Necrotizing Enterocolitis | No | 6 Participants |
| Placebo | Number of Participants With Necrotizing Enterocolitis | Yes | 0 Participants |
Secondary
Number of Participants With Need for ECMO Therapy
This is measured as Yes if an infant received ECMO treatment anytime between birth and 60 days of life; Otherwise, No. Extracorporeal membrane oxygenation (ECMO) is a treatment that uses a pump to circulate blood through an artificial lung back into the bloodstream of a very ill baby.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Need for ECMO Therapy | No | 6 Participants |
| Hydrocortisone | Number of Participants With Need for ECMO Therapy | Yes | 0 Participants |
| Placebo | Number of Participants With Need for ECMO Therapy | No | 6 Participants |
| Placebo | Number of Participants With Need for ECMO Therapy | Yes | 0 Participants |
Secondary
Number of Participants With Need for Gastronomy Tube
This is measured as Yes if a gastronomy tube was placed anytime prior to final status between birth and 60 days of life; Otherwise, No
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Need for Gastronomy Tube | No | 6 Participants |
| Hydrocortisone | Number of Participants With Need for Gastronomy Tube | Yes | 0 Participants |
| Placebo | Number of Participants With Need for Gastronomy Tube | No | 6 Participants |
| Placebo | Number of Participants With Need for Gastronomy Tube | Yes | 0 Participants |
Secondary
Number of Participants With Need for Home Oxygen
This is measured as Yes if an infant was discharged to home while on oxygen between birth and 60 days of life; Otherwise, No.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Need for Home Oxygen | No | 5 Participants |
| Hydrocortisone | Number of Participants With Need for Home Oxygen | Yes | 0 Participants |
| Placebo | Number of Participants With Need for Home Oxygen | No | 4 Participants |
| Placebo | Number of Participants With Need for Home Oxygen | Yes | 2 Participants |
Secondary
Number of Participants With Renal Insufficiency
This is measured as Yes if an infant had renal insufficieny between birth and 60 days of life; Otherwise, No. Renal insufficiency is defined as creatinine less than 2 during 7 days after first treatment
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydrocortisone | Number of Participants With Renal Insufficiency | No | 6 Participants |
| Hydrocortisone | Number of Participants With Renal Insufficiency | Yes | 0 Participants |
| Placebo | Number of Participants With Renal Insufficiency | No | 6 Participants |
| Placebo | Number of Participants With Renal Insufficiency | Yes | 0 Participants |
Secondary
Oxygenation Index
This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure divided by partial pressure of oxygen in arterial blood (PaO2), during study drug administration. A lower oxygenation index is better.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydrocortisone | Oxygenation Index | Before dose 9 | 6.6 Oxygenation Index | Standard Deviation 2.1 |
| Hydrocortisone | Oxygenation Index | Before dose 15 | 4.7 Oxygenation Index | Standard Deviation 2 |
| Hydrocortisone | Oxygenation Index | Before dose 5 | 7 Oxygenation Index | Standard Deviation 3.7 |
| Hydrocortisone | Oxygenation Index | Before dose 17 | 5.9 Oxygenation Index | Standard Deviation 3.2 |
| Hydrocortisone | Oxygenation Index | Before dose 13 | 5.8 Oxygenation Index | Standard Deviation 3 |
| Hydrocortisone | Oxygenation Index | Before dose 18 | 3.7 Oxygenation Index | — |
| Hydrocortisone | Oxygenation Index | Before dose 1 | 10.7 Oxygenation Index | Standard Deviation 6.1 |
| Placebo | Oxygenation Index | Before dose 18 | 9.1 Oxygenation Index | Standard Deviation 4.6 |
| Placebo | Oxygenation Index | Before dose 1 | 14.5 Oxygenation Index | Standard Deviation 8.6 |
| Placebo | Oxygenation Index | Before dose 5 | 14.9 Oxygenation Index | Standard Deviation 6.9 |
| Placebo | Oxygenation Index | Before dose 9 | 10.4 Oxygenation Index | Standard Deviation 5.3 |
| Placebo | Oxygenation Index | Before dose 13 | 9.2 Oxygenation Index | Standard Deviation 4.2 |
| Placebo | Oxygenation Index | Before dose 15 | 9.3 Oxygenation Index | Standard Deviation 0.8 |
| Placebo | Oxygenation Index | Before dose 17 | 7.9 Oxygenation Index | Standard Deviation 1.1 |
Secondary
Respiratory Severity
This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure during study drug administration. Higher score means more severe.
Time frame: Birth to 60 days of life
Population: The analysis population includes all randomized infants recruited from critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydrocortisone | Respiratory Severity | Before dose 9 | 531.6 Percentage of inspired oxygen * cmH2O | Standard Deviation 196.5 |
| Hydrocortisone | Respiratory Severity | Before dose 15 | 423 Percentage of inspired oxygen * cmH2O | Standard Deviation 158.8 |
| Hydrocortisone | Respiratory Severity | Before dose 5 | 518.8 Percentage of inspired oxygen * cmH2O | Standard Deviation 272.5 |
| Hydrocortisone | Respiratory Severity | Before dose 17 | 323 Percentage of inspired oxygen * cmH2O | Standard Deviation 117.8 |
| Hydrocortisone | Respiratory Severity | Before dose 13 | 414.6 Percentage of inspired oxygen * cmH2O | Standard Deviation 230 |
| Hydrocortisone | Respiratory Severity | Before dose 18 | 308.5 Percentage of inspired oxygen * cmH2O | Standard Deviation 139.3 |
| Hydrocortisone | Respiratory Severity | Before dose 1 | 726.8 Percentage of inspired oxygen * cmH2O | Standard Deviation 371 |
| Placebo | Respiratory Severity | Before dose 18 | 694.7 Percentage of inspired oxygen * cmH2O | Standard Deviation 274 |
| Placebo | Respiratory Severity | Before dose 1 | 1184.7 Percentage of inspired oxygen * cmH2O | Standard Deviation 518.7 |
| Placebo | Respiratory Severity | Before dose 5 | 1041.2 Percentage of inspired oxygen * cmH2O | Standard Deviation 432.6 |
| Placebo | Respiratory Severity | Before dose 9 | 925.8 Percentage of inspired oxygen * cmH2O | Standard Deviation 611.8 |
| Placebo | Respiratory Severity | Before dose 13 | 776.8 Percentage of inspired oxygen * cmH2O | Standard Deviation 411.2 |
| Placebo | Respiratory Severity | Before dose 15 | 899 Percentage of inspired oxygen * cmH2O | Standard Deviation 453.4 |
| Placebo | Respiratory Severity | Before dose 17 | 785.8 Percentage of inspired oxygen * cmH2O | Standard Deviation 463.2 |