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Hydrocortisone for Term Hypotension

Primary Purpose

Infant, Newborn, Diseases, Cardiovascular Insufficiency

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Hydrocortisone
Placebo
Sponsored by
NICHD Neonatal Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infant, Newborn, Diseases focused on measuring NICHD Neonatal Research Network, Mechanical ventilation, Intubation, Neurodevelopmental impairment

Eligibility Criteria

34 Weeks - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University of California - Los Angeles
  • Stanford University
  • Emory University
  • Indiana University
  • University of Iowa
  • Wayne State University
  • Children's Mercy Hospital
  • University of New Mexico
  • University of Rochester
  • RTI International
  • Duke University
  • Cincinnati Children's Medical Center
  • Case Western Reserve University
  • Research Institute at Nationwide Children's Hospital
  • University of Pennsylvania
  • University of Texas Southwestern Medical Center at Dallas
  • University of Texas Health Science Center at Houston

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hydrocortisone

Placebo

Arm Description

hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line

Saline placebo

Outcomes

Primary Outcome Measures

Death
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
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
A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected gestational age.

Secondary Outcome Measures

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.
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.
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
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.
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
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

Full Information

First Posted
September 26, 2013
Last Updated
July 2, 2021
Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT01954056
Brief Title
Hydrocortisone for Term Hypotension
Official Title
Hydrocortisone Treatment of Cardiovascular Insufficiency in Term and Late Preterm Infants: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
June 19, 2014 (Actual)
Primary Completion Date
March 20, 2018 (Actual)
Study Completion Date
March 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Newborn, Diseases, Cardiovascular Insufficiency
Keywords
NICHD Neonatal Research Network, Mechanical ventilation, Intubation, Neurodevelopmental impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydrocortisone
Arm Type
Active Comparator
Arm Description
hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline placebo
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
• 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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Death
Description
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
Title
Number of Participants With Neurodevelopmental Impairment
Description
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
Title
Number of Participants With Death or Neurodevelopmental Impairment
Description
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
Secondary Outcome Measure Information:
Title
Duration of Mechanical Ventilation
Description
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
Title
Days to Full Feeds
Description
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
Title
Number of Participants With Need for Gastronomy Tube
Description
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
Title
Duration of Oxygen Requirement
Description
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
Title
Number of Participants With Need for Home Oxygen
Description
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
Title
Hospital Length of Stay
Description
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
Title
Number of Participants With Renal Insufficiency
Description
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
Title
Number of Participants With Necrotizing Enterocolitis
Description
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
Title
Number of Participants With Need for ECMO Therapy
Description
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
Title
Number of Participants With Inotrope Exposure
Description
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.
Title
Inotrope Duration
Description
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.
Title
Maximum Inotrope Dose
Description
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.
Title
Oxygenation Index
Description
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
Title
Respiratory Severity
Description
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
Title
Number of Participants With Fluid Boluses Given
Description
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
Title
Number of Boluses Given
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
34 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele C Walsh, MD
Organizational Affiliation
Case Western Reserve University, Rainbow Babies and Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abbot R Laptook, MD
Organizational Affiliation
Brown University, Women & Infants Hospital of Rhode Island
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ron N Goldberg, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara J Stoll, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brenda B Poindexter, MD, MS
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abhik Das, PhD
Organizational Affiliation
RTI International
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Krisa P Van Meurs, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kurt Schibler, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Waldemar Carlo, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edward F Bell, MD
Organizational Affiliation
Michele C Walsh, MD Study Principal Investigator Case Western Reserve University, Rainbow Babies and Children's Hospital Seetha Shankaran, MD Study Principal Investigator Wayne State University Abbot R Laptook, MD Study Principal Investigator Brown Un
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Erika Fernandez, MD
Organizational Affiliation
University of New Mexico
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Myra Wycoff, MD
Organizational Affiliation
University of Texas, Southwestern Medical Center at Dallas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathleen A Kennedy, MD, MPH
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara Schmidt, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carl T D'Angio, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Uday Devaskar, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Leif Nelin, MD
Organizational Affiliation
Research Institute at Nationwide Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William Truog, MD
Organizational Affiliation
Children's Mercy Hospital Kansas City
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of California - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
RTI International
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Research Institute at Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://neonatal.rti.org/
Description
NICHD Neonatal Research Network site
URL
http://www.nichd.nih.gov/about/org/der/branches/ppb/Pages/overview.aspx
Description
NICHD Pregnancy & Perinatology Branch

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Hydrocortisone for Term Hypotension

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