Trial Outcomes & Findings for Hydrocortisone for Term Hypotension (NCT NCT01954056)

NCT ID: NCT01954056

Last Updated: 2021-07-06

Results Overview

This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

12 participants

Primary outcome timeframe

Birth to 22-26 months corrected gestational age

Results posted on

2021-07-06

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Hydrocortisone hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line 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	Placebo Saline placebo 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
Birth to 60 Days of Life STARTED	6	6
Birth to 60 Days of Life COMPLETED	6	6
Birth to 60 Days of Life NOT COMPLETED	0	0
Birth to 22-26 Mos. Corrected GA STARTED	6	6
Birth to 22-26 Mos. Corrected GA COMPLETED	5	6
Birth to 22-26 Mos. Corrected GA NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Hydrocortisone hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line 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	Placebo Saline placebo 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
Birth to 22-26 Mos. Corrected GA Lost to Follow-up	1	0

Baseline Characteristics

Hydrocortisone for Term Hypotension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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	Total n=12 Participants Total of all reporting groups
Age, Continuous	37.5 weeks STANDARD_DEVIATION 2.2 • n=5 Participants	39.4 weeks STANDARD_DEVIATION 1.8 • n=7 Participants	38.4 weeks STANDARD_DEVIATION 2.2 • n=5 Participants
Sex/Gender, Customized Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex/Gender, Customized Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Maternal Race Black	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Maternal Race White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Maternal Race More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Maternal Race Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Maternal Age, Continuous	32.2 years STANDARD_DEVIATION 7.6 • n=5 Participants	26.7 years STANDARD_DEVIATION 9.5 • n=7 Participants	29.4 years STANDARD_DEVIATION 8.7 • n=5 Participants
Birth weight	3415 grams STANDARD_DEVIATION 669.3 • n=5 Participants	3120.3 grams STANDARD_DEVIATION 541 • n=7 Participants	3267.7 grams STANDARD_DEVIATION 600.3 • n=5 Participants
Length	50.1 cm STANDARD_DEVIATION 2.3 • n=5 Participants	49.8 cm STANDARD_DEVIATION 1.5 • n=7 Participants	49.9 cm STANDARD_DEVIATION 1.9 • n=5 Participants
Head circumference	34.4 cm STANDARD_DEVIATION 2 • n=5 Participants	34.5 cm STANDARD_DEVIATION 3.5 • n=7 Participants	34.5 cm STANDARD_DEVIATION 2.7 • n=5 Participants
Apgar score less than 3 at 1 minute No	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Apgar score less than 3 at 1 minute Yes	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Apgar score less than 3 at 5 minutes No	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Apgar score less than 3 at 5 minutes Yes	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Apgar score less than 3 at 10 minutes No	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Apgar score less than 3 at 10 minutes Yes	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Apgar score less than 3 at 10 minutes Unknown	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Infant Outborn No	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Infant Outborn Yes	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Oxygen Yes	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Oxygen No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Bagging and Mask No	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Bagging and Mask Yes	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Chest Compression No	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Chest Compression Yes	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Intubation No	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Intubation Yes	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Medications or volume expanders No	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Medications or volume expanders Yes	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Maternal marital Status Married	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Maternal marital Status Single	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Maternal gravida	2.5 Number of pregnancies n=5 Participants	1 Number of pregnancies n=7 Participants	2 Number of pregnancies n=5 Participants
Maternal parity	2.5 Number of successful pregnancies n=5 Participants	1 Number of successful pregnancies n=7 Participants	2 Number of successful pregnancies n=5 Participants
Maternal multiple birth No	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Maternal multiple birth Yes	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Maternal prenatal care No	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Maternal prenatal care Yes	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Maternal antenatal steroids No	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Maternal antenatal steroids Yes	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Maternal documented chorioamnionitis No	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Maternal documented chorioamnionitis Yes	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Placental pathology performed No	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Placental pathology performed Yes	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Placental pathology performed Unknown	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Final mode of delivery Vaginal vertex	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Final mode of delivery Cesarean section	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Final mode of delivery Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Death No	6 Participants	6 Participants
Death Yes	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Neurodevelopmental Impairment Yes	3 Participants	3 Participants
Number of Participants With Neurodevelopmental Impairment No	3 Participants	3 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Death or Neurodevelopmental Impairment Yes	3 Participants	3 Participants
Number of Participants With Death or Neurodevelopmental Impairment No	3 Participants	3 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Duration of Mechanical Ventilation	8 Days Interval 3.0 to 10.0	11 Days Interval 3.0 to 19.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=5 Participants 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	Placebo n=3 Participants 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
Days to Full Feeds	16 Days Interval 12.0 to 23.0	18 Days Interval 8.0 to 22.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Need for Gastronomy Tube No	6 Participants	6 Participants
Number of Participants With Need for Gastronomy Tube Yes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Duration of Oxygen Requirement	15.5 Days Interval 3.0 to 33.0	18 Days Interval 5.0 to 25.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=5 Participants 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	Placebo n=6 Participants 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
Number of Participants With Need for Home Oxygen No	5 Participants	4 Participants
Number of Participants With Need for Home Oxygen Yes	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=5 Participants 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	Placebo n=5 Participants 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
Hospital Length of Stay	27 Days Interval 14.0 to 60.0	24 Days Interval 14.0 to 38.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Renal Insufficiency No	6 Participants	6 Participants
Number of Participants With Renal Insufficiency Yes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Necrotizing Enterocolitis No	5 Participants	6 Participants
Number of Participants With Necrotizing Enterocolitis Yes	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Need for ECMO Therapy No	6 Participants	6 Participants
Number of Participants With Need for ECMO Therapy Yes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Inotrope Exposure Day 3 · No	4 Participants	4 Participants
Number of Participants With Inotrope Exposure Day 3 · Yes	2 Participants	2 Participants
Number of Participants With Inotrope Exposure Day 5 · No	5 Participants	4 Participants
Number of Participants With Inotrope Exposure Day 5 · Yes	1 Participants	2 Participants
Number of Participants With Inotrope Exposure Day 7 · No	5 Participants	5 Participants
Number of Participants With Inotrope Exposure Day 7 · Yes	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Inotrope Duration	3 days Interval 1.0 to 8.0	3 days Interval 1.0 to 8.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Maximum Inotrope Dose	9.5 mcg/kg/min Standard Deviation 2.9	14.7 mcg/kg/min Standard Deviation 12.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Oxygenation Index Before dose 1	10.7 Oxygenation Index Standard Deviation 6.1	14.5 Oxygenation Index Standard Deviation 8.6
Oxygenation Index Before dose 5	7 Oxygenation Index Standard Deviation 3.7	14.9 Oxygenation Index Standard Deviation 6.9
Oxygenation Index Before dose 9	6.6 Oxygenation Index Standard Deviation 2.1	10.4 Oxygenation Index Standard Deviation 5.3
Oxygenation Index Before dose 13	5.8 Oxygenation Index Standard Deviation 3	9.2 Oxygenation Index Standard Deviation 4.2
Oxygenation Index Before dose 15	4.7 Oxygenation Index Standard Deviation 2	9.3 Oxygenation Index Standard Deviation 0.8
Oxygenation Index Before dose 17	5.9 Oxygenation Index Standard Deviation 3.2	7.9 Oxygenation Index Standard Deviation 1.1
Oxygenation Index Before dose 18	3.7 Oxygenation Index	9.1 Oxygenation Index Standard Deviation 4.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Respiratory Severity Before dose 1	726.8 Percentage of inspired oxygen * cmH2O Standard Deviation 371	1184.7 Percentage of inspired oxygen * cmH2O Standard Deviation 518.7
Respiratory Severity Before dose 5	518.8 Percentage of inspired oxygen * cmH2O Standard Deviation 272.5	1041.2 Percentage of inspired oxygen * cmH2O Standard Deviation 432.6
Respiratory Severity Before dose 9	531.6 Percentage of inspired oxygen * cmH2O Standard Deviation 196.5	925.8 Percentage of inspired oxygen * cmH2O Standard Deviation 611.8
Respiratory Severity Before dose 13	414.6 Percentage of inspired oxygen * cmH2O Standard Deviation 230	776.8 Percentage of inspired oxygen * cmH2O Standard Deviation 411.2
Respiratory Severity Before dose 15	423 Percentage of inspired oxygen * cmH2O Standard Deviation 158.8	899 Percentage of inspired oxygen * cmH2O Standard Deviation 453.4
Respiratory Severity Before dose 17	323 Percentage of inspired oxygen * cmH2O Standard Deviation 117.8	785.8 Percentage of inspired oxygen * cmH2O Standard Deviation 463.2
Respiratory Severity Before dose 18	308.5 Percentage of inspired oxygen * cmH2O Standard Deviation 139.3	694.7 Percentage of inspired oxygen * cmH2O Standard Deviation 274

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hydrocortisone n=6 Participants 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	Placebo n=6 Participants 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
Number of Participants With Fluid Boluses Given Before dose 1 · No	2 Participants	2 Participants
Number of Participants With Fluid Boluses Given Before dose 1 · Yes	4 Participants	4 Participants
Number of Participants With Fluid Boluses Given Before dose 5 · No	5 Participants	4 Participants
Number of Participants With Fluid Boluses Given Before dose 5 · Yes	1 Participants	2 Participants
Number of Participants With Fluid Boluses Given Before dose 9 · No	5 Participants	5 Participants
Number of Participants With Fluid Boluses Given Before dose 9 · Yes	1 Participants	1 Participants
Number of Participants With Fluid Boluses Given Before dose 13 · No	5 Participants	6 Participants
Number of Participants With Fluid Boluses Given Before dose 13 · Yes	1 Participants	0 Participants
Number of Participants With Fluid Boluses Given Before dose 15 · No	6 Participants	4 Participants
Number of Participants With Fluid Boluses Given Before dose 15 · Yes	0 Participants	1 Participants
Number of Participants With Fluid Boluses Given Before dose 17 · No	6 Participants	6 Participants
Number of Participants With Fluid Boluses Given Before dose 17 · Yes	0 Participants	0 Participants
Number of Participants With Fluid Boluses Given Before dose 18 · No	6 Participants	6 Participants
Number of Participants With Fluid Boluses Given Before dose 18 · Yes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Hydrocortisone n=5 Participants 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	Placebo n=5 Participants 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
Number of Boluses Given Before dose 1	3 Boluses Interval 1.0 to 7.0	3 Boluses Interval 2.0 to 8.0
Number of Boluses Given Before dose 5	2 Boluses Interval 2.0 to 2.0	1 Boluses Interval 1.0 to 1.0
Number of Boluses Given Before dose 9	2 Boluses Interval 2.0 to 2.0	1 Boluses Interval 1.0 to 1.0
Number of Boluses Given Before dose 13	1 Boluses Interval 1.0 to 1.0	—
Number of Boluses Given Before dose 15	—	1 Boluses Interval 1.0 to 1.0

Adverse Events

Hydrocortisone

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Hydrocortisone n=6 participants at risk hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line 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	Placebo n=6 participants at risk Saline placebo 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
Blood and lymphatic system disorders HYPERBILIRUBINEMIA REQUIRING EXCHANGE TRANSFUSION	16.7% 1/6 • Number of events 1 • 10 days	0.00% 0/6 • 10 days
Cardiac disorders HYPERTENSION, NEW AND SUSTAINED	16.7% 1/6 • Number of events 2 • 10 days	0.00% 0/6 • 10 days
Endocrine disorders ADRENAL INSUFFICIENCY	16.7% 1/6 • Number of events 1 • 10 days	0.00% 0/6 • 10 days

Other adverse events

Other adverse events
Measure	Hydrocortisone n=6 participants at risk hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line 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	Placebo n=6 participants at risk Saline placebo 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
Cardiac disorders ATRIAL TACHYCARDIA	0.00% 0/6 • 10 days	16.7% 1/6 • Number of events 1 • 10 days

Additional Information

Dr. Kristi Watterberg

University of New Mexico

Phone: 505-272-8609

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication policies
Publication restrictions are in place

Restriction type: OTHER