Infant, NewbornPhase 3DexamethasoneNCT00011362
Dexamethasone Therapy in VLBW Infants at Risk of CLD
A Phase 3 study testing Dexamethasone Early and Dexamethasone Late in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 13 sites in United States.
Trial summary
Infants who are on breathing support are often treated with steroids (dexamethasone); however, the best timing of therapy is not known. This trial looked at the benefits and hazards of starting dexamethasone therapy at two weeks of age and four weeks of age in premature infants. Read more about this study
- Who is it for?
- Ages 13 to 15 days
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- What is being tested?
- Dexamethasone Early and Dexamethasone Late
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 371 participants
- Where
- 13 sitesUnited States
- Study dates
- Sep 1992to Apr 1994
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 13 to 15 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 501 to 1500 grams
- 13 to 15 days old
- Respiratory-index score of greater than or equal to 2.4 that had been increasing or minimally decreasing during the previous 48 hours or a score of greater than or equal to 4.0 even if there had been improvement during the preceding 48 hours
Who cannot join
- Received glucocorticoid treatment after birth
- Had evidence or suspicious signs of sepsis as judged by the treating physician
- Major congenital anomaly of the cardiovascular, pulmonary, or central nervous system
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
Indiana University
Indianapolis, Indiana, 46202
University of Tennessee
Memphis, Tennessee, 38163
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
George Washington University
Washington D.C., District of Columbia, 20052
About this study
Official title: Randomized Clinical Trial of Dexamethasone Therapy in Very-Low-Birth-Weight Infants at Risk for Chronic Lung Disease (CLD)
Infants who are on breathing support are often treated with steroids (dexamethasone); however, the best timing of therapy is not known. This trial looked at the benefits and hazards of starting dexamethasone therapy at two weeks of age and four weeks of age in premature infants.
Read the detailed description
Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 grams) who had respiratory-index scores (mean airway pressure x the fraction of inspired oxygen) of greater than or equal 2.4 at two weeks of age. The primary outcome was the number of days from randomization to extubation not requiring reintubation (extubation score or death). The secondary outcomes were death before discharge from the hospital; the duration of assisted ventilation, supplementary oxygen therapy and hospital stay; the incidence of chronic lung disease (defined as the need for supplemental oxygen at 36 weeks postconceptional age by best obstetrical estimate) and rates of morbidity and mortality from respiratory causes during the first year. Additional secondary endpoints were hyperglycemia, hypertension, growth, bacteremia, necrotizing enterocolitis and upper GI bleeding.
The sample size of 370 was based on a 0.60 probability that the extubation score of late treatment was greater than early treatment, a 5% two-sided type 1 error, 85% power, and 10% treatment noncompliance.
Infants were randomized to either receive dexamethasone for two weeks followed by saline placebo for two weeks, or saline placebo for two weeks followed by either dexamethasone or additional placebo for two weeks (if they still met entry criteria). Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose then tapered.
The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P less than 0.001) in both groups. Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of age.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Bronchopulmonary Dysplasia
- Being tested
- Dexamethasone Early, Dexamethasone Late
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Dexamethasone, Glucocorticoids, Respiratory Distress Syndrome, Respiratory insufficiency, Steroids
- Medical subject headings
- Premature Birth, Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone EarlyDrug
Tapering course of dexamethasone in doses given twice a day (0.25 mg per kilogram of body weight per dose for five days, then 0.15 mg, 0.07 mg, and 0.03 mg per kilogram per dose for three days each), followed by two weeks of saline.
Dexamethasone LateDrug
Saline for two weeks, followed by either the same tapering two-week course of dexamethasone given to the first group, if the respiratory-index score was >=2.4 on treatment day 14, or an additional two weeks of saline
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone | Active comparator | Dexamethasone Receives: Drug: Dexamethasone Early; Drug: Dexamethasone Late |
| Placebo | Placebo comparator | Saline Receives: Drug: Dexamethasone Early; Drug: Dexamethasone Late |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days from randomization to ventilator independence, defined as extubation not requiring reintubation, or extubation followed by elective reintubation for seven days or less so that the infant could undergo a surgical procedure
Measured: At hospital discharge
Secondary outcomes (6)
Death before discharge from the hospital
Measured: At hospital discharge
Duration of assisted ventilation
Measured: At hospital discharge
Duration of supplemental oxygen therapy
Measured: At hospital discharge
Duration of hospital stay
Measured: At hospital discharge
Incidence of chronic lung disease
Measured: At hospital discharge
Morbidity and mortality from respiratory causes during the first year
Measured: 12 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2001 (estimated)
- Study startSep 1992
- Primary completionJan 1994
- Study completionApr 1994
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Infant, NewbornStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 371 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Lu-Ann Papile, MD, Principal investigator, University of New MexicoJon E. Tyson, MD MPH, Principal investigator, University of Texas Southwestern Medical CenterBarbara J. Stoll, MD, Principal investigator, Emory UniversityEdward F. Donovan, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiCharles R. Bauer, MD, Principal investigator, University of MiamiSheldon B. Korones, MD, Principal investigator, University of TennesseeJames A. Lemons, MD, Principal investigator, Indiana UniversityAvroy A. Fanaroff, MD, Principal investigator, Rainbow Babies & Children's Hospital, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011362
- Sponsor's protocol ID
- NICHD-NRN-0005
- Other IDs
- U10HD027881, U10HD021373, U10HD027851, U10HD027853, U10HD021397, U01HD019897, U10HD021415, U10HD027856
- Acronym
- Dexamethasone
- Status last verified
- Mar 2019
- First submitted
- 15 Feb 2001
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Papile LA, Tyson JE, Stoll BJ, Wright LL, Donovan EF, Bauer CR, Krause-Steinrauf H, Verter J, Korones SB, Lemons JA, Fanaroff AA, Stevenson DK. A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants. N Engl J Med. 1998 Apr 16;338(16):1112-8. doi: 10.1056/NEJM199804163381604.
PubMed 9545359Leitch CA, Ahlrichs J, Karn C, Denne SC. Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease. Pediatr Res. 1999 Jul;46(1):109-13. doi: 10.1203/00006450-199907000-00018.
PubMed 10400143Stoll BJ, Temprosa M, Tyson JE, Papile LA, Wright LL, Bauer CR, Donovan EF, Korones SB, Lemons JA, Fanaroff AA, Stevenson DK, Oh W, Ehrenkranz RA, Shankaran S, Verter J. Dexamethasone therapy increases infection in very low birth weight infants. Pediatrics. 1999 Nov;104(5):e63. doi: 10.1542/peds.104.5.e63.
PubMed 10545589Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Pediatrics. 2006 May;117(5):1503-10. doi: 10.1542/peds.2005-1749.
PubMed 16651303Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics. 2008 Feb;121(2):289-96. doi: 10.1542/peds.2007-1103.
PubMed 18245420
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial of Dexamethasone Therapy in Very-Low-Birth-Weight Infants at Risk for Chronic Lung Disease (CLD)
- ClinicalTrials.gov ID
- NCT00011362
- Acronym / sponsor ID
- Dexamethasone / NICHD-NRN-0005
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Bronchopulmonary Dysplasia
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Dexamethasone, Glucocorticoids, Respiratory Distress Syndrome, Respiratory insufficiency, Steroids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 371 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Sep 1992
- Primary completion
- Jan 1994 (actual)
- Study completion
- Apr 1994 (actual)
- First posted
- 19 Feb 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infants who are on breathing support are often treated with steroids (dexamethasone); however, the best timing of therapy is not known. This trial looked at the benefits and hazards of starting dexamethasone therapy at two weeks of age and four weeks of age in premature infants.
Detailed description
Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 grams) who had respiratory-index scores (mean airway pressure x the fraction of inspired oxygen) of greater than or equal 2.4 at two weeks of age. The primary outcome was the number of days from randomization to extubation not requiring reintubation (extubation score or death). The secondary outcomes were death before discharge from the hospital; the duration of assisted ventilation, supplementary oxygen therapy and hospital stay; the incidence of chronic lung disease (defined as the need for supplemental oxygen at 36 weeks postconceptional age by best obstetrical estimate) and rates of morbidity and mortality from respiratory causes during the first year. Additional secondary endpoints were hyperglycemia, hypertension, growth, bacteremia, necrotizing enterocolitis and upper GI bleeding.
The sample size of 370 was based on a 0.60 probability that the extubation score of late treatment was greater than early treatment, a 5% two-sided type 1 error, 85% power, and 10% treatment noncompliance.
Infants were randomized to either receive dexamethasone for two weeks followed by saline placebo for two weeks, or saline placebo for two weeks followed by either dexamethasone or additional placebo for two weeks (if they still met entry criteria). Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose then tapered.
The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P less than 0.001) in both groups. Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of age.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone | Active comparator | Drug: Dexamethasone Early, Drug: Dexamethasone LateDexamethasone |
| Placebo | Placebo comparator | Drug: Dexamethasone Early, Drug: Dexamethasone LateSaline |
Who may qualify
- Ages
- 13 to 15 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 501 to 1500 grams
- 13 to 15 days old
- Respiratory-index score of greater than or equal to 2.4 that had been increasing or minimally decreasing during the previous 48 hours or a score of greater than or equal to 4.0 even if there had been improvement during the preceding 48 hours
Key exclusion criteria (3 listed)
- Received glucocorticoid treatment after birth
- Had evidence or suspicious signs of sepsis as judged by the treating physician
- Major congenital anomaly of the cardiovascular, pulmonary, or central nervous system
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 |
|---|---|---|
| Dexamethasone EarlyTapering course of dexamethasone in doses given twice a day (0.25 mg per kilogram of body weight per dose for five days, then 0.15 mg, 0.07 mg, and 0.03 mg per kilogram per dose for three days each), followed by two weeks of saline. | Drug | Dexamethasone, Placebo |
| Dexamethasone LateSaline for two weeks, followed by either the same tapering two-week course of dexamethasone given to the first group, if the respiratory-index score was >=2.4 on treatment day 14, or an additional two weeks of saline | Drug | Dexamethasone, Placebo |
Primary outcome
Number of days from randomization to ventilator independence, defined as extubation not requiring reintubation, or extubation followed by elective reintubation for seven days or less so that the infant could undergo a surgical procedure
Time frame: At hospital discharge
6 secondary outcomes
Death before discharge from the hospital
Time frame: At hospital discharge
Duration of assisted ventilation
Time frame: At hospital discharge
Duration of supplemental oxygen therapy
Time frame: At hospital discharge
Duration of hospital stay
Time frame: At hospital discharge
Incidence of chronic lung disease
Time frame: At hospital discharge
Morbidity and mortality from respiratory causes during the first year
Time frame: 12 months of age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
- Results publication: PubMed 9545359Papile LA, Tyson JE, Stoll BJ, Wright LL, Donovan EF, Bauer CR, Krause-Steinrauf H, Verter J, Korones SB, Lemons JA, Fanaroff AA, Stevenson DK. A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants. N Engl J Med. 1998 Apr 16;338(16):1112-8. doi: 10.1056/NEJM199804163381604.
- Results publication: PubMed 10400143Leitch CA, Ahlrichs J, Karn C, Denne SC. Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease. Pediatr Res. 1999 Jul;46(1):109-13. doi: 10.1203/00006450-199907000-00018.
- Results publication: PubMed 10545589Stoll BJ, Temprosa M, Tyson JE, Papile LA, Wright LL, Bauer CR, Donovan EF, Korones SB, Lemons JA, Fanaroff AA, Stevenson DK, Oh W, Ehrenkranz RA, Shankaran S, Verter J. Dexamethasone therapy increases infection in very low birth weight infants. Pediatrics. 1999 Nov;104(5):e63. doi: 10.1542/peds.104.5.e63.
- Results publication: PubMed 16651303Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Pediatrics. 2006 May;117(5):1503-10. doi: 10.1542/peds.2005-1749.
- Results publication: PubMed 18245420Lee BH, Stoll BJ, McDonald SA, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics. 2008 Feb;121(2):289-96. doi: 10.1542/peds.2007-1103.
- Click here for more information on the NICHD Neonatal Research Network.Link 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.
Lu-Ann Papile, MD principal investigator
University of New Mexico
Jon E. Tyson, MD MPH principal investigator
University of Texas Southwestern Medical Center
Barbara J. Stoll, MD principal investigator
Emory University
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone Early and Dexamethasone Late in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 13 sites 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 3 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 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of days from randomization to ventilator independence, defined as extubation not requiring reintubation, or extubation followed by elective reintubation for seven days or less so that the infant could undergo a surgical procedure (time frame: At hospital discharge). 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 NCT00011362, which also lists 5 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 22 Mar 2019.