Dexamethasone Therapy in VLBW Infants at Risk of CLD

NCT ID: NCT00011362

Last Updated: 2019-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

371 participants

Study Classification

INTERVENTIONAL

Study Start Date

1992-09-30

Study Completion Date

1994-04-30

Brief Summary

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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

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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

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Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Bronchopulmonary Dysplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Dexamethasone

Dexamethasone

Group Type ACTIVE_COMPARATOR

Dexamethasone Early

Intervention Type DRUG

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 Late

Intervention Type DRUG

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

Placebo

Saline

Group Type PLACEBO_COMPARATOR

Dexamethasone Early

Intervention Type DRUG

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 Late

Intervention Type DRUG

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

Interventions

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Dexamethasone Early

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.

Intervention Type DRUG

Dexamethasone Late

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

13 Days

Maximum Eligible Age

15 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

NICHD Neonatal Research Network

NETWORK

Sponsor Role lead

Responsible Party

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University of New Mexico

Principal Investigators

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Lu-Ann Papile, MD

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Jon E. Tyson, MD MPH

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Barbara J. Stoll, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Edward F. Donovan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Charles R. Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Sheldon B. Korones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tennessee

James A. Lemons, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Avroy A. Fanaroff, MD

Role: PRINCIPAL_INVESTIGATOR

Rainbow Babies & Children's Hospital, Case Western Reserve University

David K. Stevenson, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

William Oh, MD

Role: PRINCIPAL_INVESTIGATOR

Women & Infants' Hospital, Brown University

Richard A. Ehrenkranz, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Stanford University

Palo Alto, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

George Washington University

Washington D.C., District of Columbia, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status

University of Tennessee

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 9545359 (View on PubMed)

Leitch 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.

Reference Type RESULT
PMID: 10400143 (View on PubMed)

Stoll 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.

Reference Type RESULT
PMID: 10545589 (View on PubMed)

Lee 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.

Reference Type RESULT
PMID: 16651303 (View on PubMed)

Lee 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.

Reference Type RESULT
PMID: 18245420 (View on PubMed)

Related Links

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http://neonatal.rti.org/

Click here for more information on the NICHD Neonatal Research Network.

Other Identifiers

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U10HD027881

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021373

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027853

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021397

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HD019897

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021415

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021364

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027880

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021385

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000997

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR008084

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR006022

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHD-NRN-0005

Identifier Type: -

Identifier Source: org_study_id

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