Dexamethasone Therapy in VLBW Infants at Risk of CLD

Study Overview
=================
Brief 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.

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

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

Intervention / Treatment
-----------------
* Drug: Dexamethasone Early
* Drug: Dexamethasone Late


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 13 Days
Maximum Age: 15 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone<br>Dexamethasone | Drug: Dexamethasone Early<br>* 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.<br>Drug: Dexamethasone Late<br>* 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<br>|
| Placebo Comparator: Placebo<br>Saline | Drug: Dexamethasone Early<br>* 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.<br>Drug: Dexamethasone Late<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death before discharge from the hospital |  | At hospital discharge | 
| Duration of assisted ventilation |  | At hospital discharge | 
| Duration of supplemental oxygen therapy |  | At hospital discharge | 
| Duration of hospital stay |  | At hospital discharge | 
| Incidence of chronic lung disease |  | At hospital discharge | 
| Morbidity and mortality from respiratory causes during the first year |  | 12 months of age | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Dexamethasone, Glucocorticoids, Respiratory Distress Syndrome, Respiratory insufficiency, Steroids