Dexamethasone Therapy in VLBW Infants at Risk of CLD

Bronchopulmonary Dysplasia Clinical Trial

— Dexamethasone  

Official title:

Randomized Clinical Trial of Dexamethasone Therapy in Very-Low-Birth-Weight Infants at Risk for Chronic Lung Disease (CLD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00011362
• Other study ID #: NICHD-NRN-0005
• Secondary ID: U10HD027881U10HD
• Status: Completed
• Phase: Phase 3
• Start date: September 1992
• Est. completion date: April 1994

Study information

• Verified date: March 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 371
• Est. completion date: April 1994
• Est. primary completion date: January 1994
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Days

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• 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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	George Washington University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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):15 — View Citation

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. Pedi — View Citation

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. — View Citation

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 — View Citation

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. Pediatric — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		At hospital discharge
Secondary	Death before discharge from the hospital		At hospital discharge
Secondary	Duration of assisted ventilation		At hospital discharge
Secondary	Duration of supplemental oxygen therapy		At hospital discharge
Secondary	Duration of hospital stay		At hospital discharge
Secondary	Incidence of chronic lung disease		At hospital discharge
Secondary	Morbidity and mortality from respiratory causes during the first year		12 months of age

External Links

•   Click here for more information on the NICHD Neonatal Research Network.
•   Click here for the Cochrane neonatal review, "Postnatal corticosteroids for prevention of chronic lung disease in the preterm infant: moderately early treatment."
•   Click here for the Cochrane neonatal review, "Postnatal corticosteroids for prevention of chronic lung diseasein the preterm infant: early treatment."
•   Click here for the Cochrane Neonatal Review, "Postnatal corticosteroids in preterm infants with chronic lung disease: late treatment."