Hydrocortisone for Term Hypotension

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hydrocortisone Treatment of Cardiovascular Insufficiency in Term and Late Preterm Infants: A Randomized Controlled Trial

Conditions
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Infant, Newborn, Diseases, Cardiovascular Insufficiency

Intervention / Treatment
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* Drug: Hydrocortisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 34 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydrocortisone<br>hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line | Drug: Hydrocortisone<br>* • 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<br>|
| Placebo Comparator: Placebo<br>Saline placebo | Drug: Placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No. | Birth to 22-26 months corrected gestational age | 
| 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. | Birth to 22-26 months corrected gestational age | 
| 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. | Birth to 22-26 months corrected gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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 | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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 | Birth to 60 days of life | 
| 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 | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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. | 24 hours prior to study drug administration through 3 days post study drug administration. | 
| 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. | 24 hours prior to study drug administration through 3 days post study drug administration. | 
| 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. | From start of study drug administration (7 days) through 3 days post study drug administration. | 
| 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. | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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. | Birth to 60 days of life | 
| 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 | Birth to 60 days of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Mechanical ventilation, Intubation, Neurodevelopmental impairment