Dexamethasone Therapy in VLBW Infants at Risk of CLD
Condition: Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Bronchopulmonary Dysplasia
MeSH terms: Bronchopulmonary Dysplasia; Birth Weight
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Dexamethasone Early; Dexamethasone Late
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Prematurity; Dexamethasone; Glucocorticoids; Respiratory Distress Syndrome; Respiratory insufficiency; Steroids