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
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
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
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
6
5
Birth to 22-26 Mos. Corrected GA
NOT COMPLETED
0
1

Reasons for withdrawal

Reasons for withdrawal
Measure
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
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
Birth to 22-26 Mos. Corrected GA
Lost to Follow-up
0
1

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=99 Participants
39.4 weeks
STANDARD_DEVIATION 1.8 • n=107 Participants
38.4 weeks
STANDARD_DEVIATION 2.2 • n=206 Participants
Sex/Gender, Customized
Male
4 Participants
n=99 Participants
2 Participants
n=107 Participants
6 Participants
n=206 Participants
Sex/Gender, Customized
Female
2 Participants
n=99 Participants
4 Participants
n=107 Participants
6 Participants
n=206 Participants
Race/Ethnicity, Customized
Hispanic or Latino
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
3 Participants
n=99 Participants
5 Participants
n=107 Participants
8 Participants
n=206 Participants
Race/Ethnicity, Customized
Unknown or Not Reported
2 Participants
n=99 Participants
0 Participants
n=107 Participants
2 Participants
n=206 Participants
Maternal Race
Black
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Maternal Race
White
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Maternal Race
More than one race
0 Participants
n=99 Participants
1 Participants
n=107 Participants
1 Participants
n=206 Participants
Maternal Race
Unknown or Not Reported
0 Participants
n=99 Participants
1 Participants
n=107 Participants
1 Participants
n=206 Participants
Maternal Age, Continuous
32.2 years
STANDARD_DEVIATION 7.6 • n=99 Participants
26.7 years
STANDARD_DEVIATION 9.5 • n=107 Participants
29.4 years
STANDARD_DEVIATION 8.7 • n=206 Participants
Birth weight
3415 grams
STANDARD_DEVIATION 669.3 • n=99 Participants
3120.3 grams
STANDARD_DEVIATION 541 • n=107 Participants
3267.7 grams
STANDARD_DEVIATION 600.3 • n=206 Participants
Length
50.1 cm
STANDARD_DEVIATION 2.3 • n=99 Participants
49.8 cm
STANDARD_DEVIATION 1.5 • n=107 Participants
49.9 cm
STANDARD_DEVIATION 1.9 • n=206 Participants
Head circumference
34.4 cm
STANDARD_DEVIATION 2 • n=99 Participants
34.5 cm
STANDARD_DEVIATION 3.5 • n=107 Participants
34.5 cm
STANDARD_DEVIATION 2.7 • n=206 Participants
Apgar score less than 3 at 1 minute
No
2 Participants
n=99 Participants
4 Participants
n=107 Participants
6 Participants
n=206 Participants
Apgar score less than 3 at 1 minute
Yes
4 Participants
n=99 Participants
2 Participants
n=107 Participants
6 Participants
n=206 Participants
Apgar score less than 3 at 5 minutes
No
5 Participants
n=99 Participants
6 Participants
n=107 Participants
11 Participants
n=206 Participants
Apgar score less than 3 at 5 minutes
Yes
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Apgar score less than 3 at 10 minutes
No
3 Participants
n=99 Participants
3 Participants
n=107 Participants
6 Participants
n=206 Participants
Apgar score less than 3 at 10 minutes
Yes
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Apgar score less than 3 at 10 minutes
Unknown
3 Participants
n=99 Participants
3 Participants
n=107 Participants
6 Participants
n=206 Participants
Infant Outborn
No
4 Participants
n=99 Participants
2 Participants
n=107 Participants
6 Participants
n=206 Participants
Infant Outborn
Yes
2 Participants
n=99 Participants
4 Participants
n=107 Participants
6 Participants
n=206 Participants
Oxygen
Yes
6 Participants
n=99 Participants
6 Participants
n=107 Participants
12 Participants
n=206 Participants
Oxygen
No
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Bagging and Mask
No
1 Participants
n=99 Participants
2 Participants
n=107 Participants
3 Participants
n=206 Participants
Bagging and Mask
Yes
5 Participants
n=99 Participants
4 Participants
n=107 Participants
9 Participants
n=206 Participants
Chest Compression
No
5 Participants
n=99 Participants
5 Participants
n=107 Participants
10 Participants
n=206 Participants
Chest Compression
Yes
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Intubation
No
4 Participants
n=99 Participants
1 Participants
n=107 Participants
5 Participants
n=206 Participants
Intubation
Yes
2 Participants
n=99 Participants
5 Participants
n=107 Participants
7 Participants
n=206 Participants
Medications or volume expanders
No
5 Participants
n=99 Participants
3 Participants
n=107 Participants
8 Participants
n=206 Participants
Medications or volume expanders
Yes
1 Participants
n=99 Participants
3 Participants
n=107 Participants
4 Participants
n=206 Participants
Maternal marital Status
Married
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Maternal marital Status
Single
5 Participants
n=99 Participants
5 Participants
n=107 Participants
10 Participants
n=206 Participants
Maternal gravida
2.5 Number of pregnancies
n=99 Participants
1 Number of pregnancies
n=107 Participants
2 Number of pregnancies
n=206 Participants
Maternal parity
2.5 Number of successful pregnancies
n=99 Participants
1 Number of successful pregnancies
n=107 Participants
2 Number of successful pregnancies
n=206 Participants
Maternal multiple birth
No
6 Participants
n=99 Participants
6 Participants
n=107 Participants
12 Participants
n=206 Participants
Maternal multiple birth
Yes
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Maternal prenatal care
No
2 Participants
n=99 Participants
1 Participants
n=107 Participants
3 Participants
n=206 Participants
Maternal prenatal care
Yes
4 Participants
n=99 Participants
5 Participants
n=107 Participants
9 Participants
n=206 Participants
Maternal antenatal steroids
No
6 Participants
n=99 Participants
6 Participants
n=107 Participants
12 Participants
n=206 Participants
Maternal antenatal steroids
Yes
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Maternal documented chorioamnionitis
No
5 Participants
n=99 Participants
6 Participants
n=107 Participants
11 Participants
n=206 Participants
Maternal documented chorioamnionitis
Yes
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Placental pathology performed
No
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Placental pathology performed
Yes
2 Participants
n=99 Participants
3 Participants
n=107 Participants
5 Participants
n=206 Participants
Placental pathology performed
Unknown
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Final mode of delivery
Vaginal vertex
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Final mode of delivery
Cesarean section
3 Participants
n=99 Participants
3 Participants
n=107 Participants
6 Participants
n=206 Participants
Final mode of delivery
Unknown
0 Participants
n=99 Participants
1 Participants
n=107 Participants
1 Participants
n=206 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

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 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

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.

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

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 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

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.

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

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 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

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 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

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 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

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 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

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 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

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 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

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 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.

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 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.

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 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.

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 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

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 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

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 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

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 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

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.

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

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