Bronchopulmonary DysplasiaPhase 2NCT00167544
Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants
A Phase 2 study testing Hydrocortisone in people with Bronchopulmonary Dysplasia and Encephalomalacia, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine whether treatment of very preterm infants at high-risk for lung and brain injury with low dose hydrocortisone results in improved pulmonary and neurologic outcomes. Read more about this study
- Who is it for?
- Ages 1 week to 3 weeks
- Conditions the study is for
- Bronchopulmonary Dysplasia, Encephalomalacia, Premature Birth
- What is being tested?
- Hydrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Nov 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week to 3 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient in the Memorial Hermann Children's Hospital (MHCH) neonatal intensive care unit with a birth weight ≤ 1000 grams.
- Ventilator-dependent between 10 and 21 days of age.
- Respiratory index score (RIS: mean airway pressure x fraction of inspired oxygen) of ≥ 2.0 that is increasing or stable for the previous 24 hours or a RIS ≥ 3.0 if improvement noted in the past 24 hours.
Who cannot join
- Prior postnatal steroid treatment.
- Evidence of sepsis or necrotizing enterocolitis.
- Known major congenital anomalies of the cardiopulmonary or central nervous system.
- Infants being treated with indomethacin or those likely to require treatment in the next 7 days as judged by the treating physician.
- Inability or unwillingness of parent or legal guardian/representative to give written informed consent.
- Gestational age < 23 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 432025
About this study
Official title: A Randomized Trial of Hydrocortisone in Very Preterm Infants at High Risk for Neurologic and Pulmonary Impairments
The purpose of this study is to determine whether treatment of very preterm infants at high-risk for lung and brain injury with low dose hydrocortisone results in improved pulmonary and neurologic outcomes.
Read the detailed description
Hypothesis: Among extremely low birth weight infants (ELBW; BW ≤ 1000 g) at high risk for bronchopulmonary dysplasia (BPD) and neurologic impairments, those infants randomized to seven days of hydrocortisone will demonstrate increased total cerebral tissue volumes as compared to infants randomized to placebo.
Specific Aims: 1) To perform a pilot blinded randomized controlled trial of a 7-day regimen of low dose hydrocortisone in ELBW infants at high risk for BPD and neurosensory impairments and assess its effect on cerebral tissue volumes. 2) Evaluate and report 2 year neurodevelopmental outcomes.
Background and Significance: Bronchopulmonary dysplasia is a disease of arrested lung development and lung inflammation. It is primarily seen in ELBW infants. Neurological delay, including cerebral palsy and mental retardation, affect up to 40%-50% of surviving ELBW infants. BPD is an important risk factor for such neurological delay. Postnatal administration of corticosteroids to ventilated preterm neonates results in a reduced risk of developing BPD. Postnatal corticosteroids however have shown harmful effects on the brain and can lead to increased rates of cerebral palsy and learning problems. This effect has primarily been seen with dexamethasone when high doses were given in the first week of life. Beyond the first week of life, there is insufficient information on the effects of steroids on the brain. Steroids other than dexamethasone, in much lower doses have been shown to improve short term lung function with minimal short-term side effects. A review study of all steroid trials for BPD shows that when given to a high risk group of infants (> 50% risk of BPD) steroids protect the brain and reduce rates of cerebral palsy. The American and Canadian Pediatric societies and respected researchers have commented on the urgent need for more trials of other corticosteroids at lower doses started after the first week of life to evaluate their short and long-term pulmonary and neurological benefits and risks.
Research Design and Methods:
- Inclusion \& Exclusion Criteria: See below.
- Procedures: Consented eligible patients will be randomly assigned to receive hydrocortisone in a tapering schedule over 7 days or placebo (comparison group). Study drug will be given every 12 hours IV with only study pharmacist aware of assignment. The patient's anatomic brain MRI (routinely done on all ELBW infants at 38 weeks post-menstrual age) will be further processed by the masked study investigators to derive total and regional brain volumes. Administration of indomethacin or dexamethasone to enrolled infants will be closely monitored and regulated throughout the trial period. Indomethacin use during study period is contraindicated. Dexamethasone (or other steroid) use will be restricted to ELBW infants on high ventilator settings (RIS > 10) after 28 days of life. All other procedures will be per routine care. Blinded developmental follow-up at two years, already currently performed for all ELBW infants at MHCH, will be analyzed and reported for all study infants.
- Being tested
- Hydrocortisone, Placebo
- Keywords
- Bronchopulmonary Dysplasia, Encephalomalacia, Brain injury, Neurosensory impairment, Corticosteroids, Anti-Inflammatory Agents, Extremely Low Birth Weight (ELBW) infants, Premature Birth, Magnetic Resonance Imaging
- Medical subject headings
- Bronchopulmonary Dysplasia, Encephalomalacia, Premature Birth, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Hydrocortisone 3 mg/kg/d divided q 12h IV/PO tapered over 7 days
PlaceboDrug
Saline
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 1. Tapering dose of hydrocortisone every 12 h over 7 day period Receives: Drug: Hydrocortisone |
| 2 | Placebo comparator | 2. Identical-appearing saline placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Cerebral Volume as Measured by Volumetric Brain MRI
Total cerebral volume included all brain gray matter and white matter, including cerebellum.
Measured: 38 weeks postmenstrual age (PMA)
Secondary outcomes (4)
Regional Brain Volumes
Cerebral white matter volume
Measured: 38-weeks postmenstrual age
Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure)
Measured: Up to 36 weeks PMA
Duration of Oxygen Requirement
Measured: Up to 36 weeks PMA
Survival Without Severe Bronchopulmonary Dysplasia (BPD)
Using the NIH Consensus definition (Jobe A, 2001)
Measured: 36 weeks postmenstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startNov 2005
- Primary completionJan 2009
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Nehal Parikh, Nationwide Children's Hospital
- Investigators
- Nehal A. Parikh, D.O., M.S., Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167544
- Sponsor's protocol ID
- K23NS048152
- Other IDs
- K23NS048152, HSC-MS-05-0218
- Status last verified
- Jul 2013
- First submitted
- 9 Sep 2005
- Last updated
- 30 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Parikh NA, Lasky RE, Kennedy KA, Moya FR, Hochhauser L, Romo S, Tyson JE. Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. Pediatrics. 2007 Feb;119(2):265-72. doi: 10.1542/peds.2006-1354.
PubMed 17272615Yu X, Zhang Y, Lasky RE, Datta S, Parikh NA, Narayana PA. Comprehensive brain MRI segmentation in high risk preterm newborns. PLoS One. 2010 Nov 8;5(11):e13874. doi: 10.1371/journal.pone.0013874.
PubMed 21079730Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr. 2013 Apr;162(4):685-690.e1. doi: 10.1016/j.jpeds.2012.09.054. Epub 2012 Nov 8.
PubMed 23140612Parikh NA, Kennedy KA, Lasky RE, Tyson JE. Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone. PLoS One. 2015 Sep 16;10(9):e0137051. doi: 10.1371/journal.pone.0137051. eCollection 2015.
PubMed 26376074
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Hydrocortisone in Very Preterm Infants at High Risk for Neurologic and Pulmonary Impairments
- ClinicalTrials.gov ID
- NCT00167544
- Acronym / sponsor ID
- K23NS048152
- Keywords
- Bronchopulmonary Dysplasia, Encephalomalacia, Brain injury, Neurosensory impairment, Corticosteroids, Anti-Inflammatory Agents, Extremely Low Birth Weight (ELBW) infants, Premature Birth
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Nov 2005
- Primary completion
- Jan 2009 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Posted 30 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether treatment of very preterm infants at high-risk for lung and brain injury with low dose hydrocortisone results in improved pulmonary and neurologic outcomes.
Detailed description
Hypothesis: Among extremely low birth weight infants (ELBW; BW ≤ 1000 g) at high risk for bronchopulmonary dysplasia (BPD) and neurologic impairments, those infants randomized to seven days of hydrocortisone will demonstrate increased total cerebral tissue volumes as compared to infants randomized to placebo.
Specific Aims: 1) To perform a pilot blinded randomized controlled trial of a 7-day regimen of low dose hydrocortisone in ELBW infants at high risk for BPD and neurosensory impairments and assess its effect on cerebral tissue volumes. 2) Evaluate and report 2 year neurodevelopmental outcomes.
Background and Significance: Bronchopulmonary dysplasia is a disease of arrested lung development and lung inflammation. It is primarily seen in ELBW infants. Neurological delay, including cerebral palsy and mental retardation, affect up to 40%-50% of surviving ELBW infants. BPD is an important risk factor for such neurological delay. Postnatal administration of corticosteroids to ventilated preterm neonates results in a reduced risk of developing BPD. Postnatal corticosteroids however have shown harmful effects on the brain and can lead to increased rates of cerebral palsy and learning problems. This effect has primarily been seen with dexamethasone when high doses were given in the first week of life. Beyond the first week of life, there is insufficient information on the effects of steroids on the brain. Steroids other than dexamethasone, in much lower doses have been shown to improve short term lung function with minimal short-term side effects. A review study of all steroid trials for BPD shows that when given to a high risk group of infants (> 50% risk of BPD) steroids protect the brain and reduce rates of cerebral palsy. The American and Canadian Pediatric societies and respected researchers have commented on the urgent need for more trials of other corticosteroids at lower doses started after the first week of life to evaluate their short and long-term pulmonary and neurological benefits and risks.
Research Design and Methods:
- Inclusion \& Exclusion Criteria: See below.
- Procedures: Consented eligible patients will be randomly assigned to receive hydrocortisone in a tapering schedule over 7 days or placebo (comparison group). Study drug will be given every 12 hours IV with only study pharmacist aware of assignment. The patient's anatomic brain MRI (routinely done on all ELBW infants at 38 weeks post-menstrual age) will be further processed by the masked study investigators to derive total and regional brain volumes. Administration of indomethacin or dexamethasone to enrolled infants will be closely monitored and regulated throughout the trial period. Indomethacin use during study period is contraindicated. Dexamethasone (or other steroid) use will be restricted to ELBW infants on high ventilator settings (RIS > 10) after 28 days of life. All other procedures will be per routine care. Blinded developmental follow-up at two years, already currently performed for all ELBW infants at MHCH, will be analyzed and reported for all study infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Hydrocortisone1. Tapering dose of hydrocortisone every 12 h over 7 day period |
| 2 | Placebo comparator | Drug: Placebo2. Identical-appearing saline placebo |
Who may qualify
- Ages
- 1 week to 3 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Patient in the Memorial Hermann Children's Hospital (MHCH) neonatal intensive care unit with a birth weight ≤ 1000 grams.
- Ventilator-dependent between 10 and 21 days of age.
- Respiratory index score (RIS: mean airway pressure x fraction of inspired oxygen) of ≥ 2.0 that is increasing or stable for the previous 24 hours or a RIS ≥ 3.0 if improvement noted in the past 24 hours.
Key exclusion criteria (6 listed)
- Prior postnatal steroid treatment.
- Evidence of sepsis or necrotizing enterocolitis.
- Known major congenital anomalies of the cardiopulmonary or central nervous system.
- Infants being treated with indomethacin or those likely to require treatment in the next 7 days as judged by the treating physician.
- Inability or unwillingness of parent or legal guardian/representative to give written informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneHydrocortisone 3 mg/kg/d divided q 12h IV/PO tapered over 7 days | Drug | 1 |
| PlaceboSaline | Drug | 2 |
Primary outcome
Total Cerebral Volume as Measured by Volumetric Brain MRI
Time frame: 38 weeks postmenstrual age (PMA)
Total cerebral volume included all brain gray matter and white matter, including cerebellum.
4 secondary outcomes
Regional Brain Volumes
Time frame: 38-weeks postmenstrual age
Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure)
Time frame: Up to 36 weeks PMA
Duration of Oxygen Requirement
Time frame: Up to 36 weeks PMA
Survival Without Severe Bronchopulmonary Dysplasia (BPD)
Time frame: 36 weeks postmenstrual age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17272615Parikh NA, Lasky RE, Kennedy KA, Moya FR, Hochhauser L, Romo S, Tyson JE. Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. Pediatrics. 2007 Feb;119(2):265-72. doi: 10.1542/peds.2006-1354.
- Background: PubMed 21079730Yu X, Zhang Y, Lasky RE, Datta S, Parikh NA, Narayana PA. Comprehensive brain MRI segmentation in high risk preterm newborns. PLoS One. 2010 Nov 8;5(11):e13874. doi: 10.1371/journal.pone.0013874.
- Results publication: PubMed 23140612Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr. 2013 Apr;162(4):685-690.e1. doi: 10.1016/j.jpeds.2012.09.054. Epub 2012 Nov 8.
- Derived from this study: PubMed 26376074Parikh NA, Kennedy KA, Lasky RE, Tyson JE. Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone. PLoS One. 2015 Sep 16;10(9):e0137051. doi: 10.1371/journal.pone.0137051. eCollection 2015.
- Patient information page - Bronchopulmonary DysplasiaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nehal A. Parikh, D.O., M.S. principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydrocortisone in people with Bronchopulmonary Dysplasia and Encephalomalacia, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Cerebral Volume as Measured by Volumetric Brain MRI (time frame: 38 weeks postmenstrual age (PMA)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00167544, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2013.