Bronchopulmonary Dysplasia, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Respiratory Distress Syndrome
Conditions
Keywords
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Chronic Lung Disease (CLD), Dexamethasone, Glucocorticoids, Respiration, Artificial, Mechanical ventilation, Respiratory Insufficiency
Brief summary
This multicenter clinical trial tested whether minimal ventilation decreases death or BPD. Infants with birth weight 501g to 1000g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide \[PCO(2)\] target \>52 mm Hg) or routine ventilation (PCO(2) target \<48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. The infants' neurodevelopment was evaluated at 18-22 months corrected age.
Detailed description
Chronic lung disease (CLD), also known as bronchopulmonary dysplasia (BPD), in very premature infants has been associated with mechanical ventilation and relative adrenal insufficiency. This multicenter clinical trial tested whether minimal ventilation decreases death or BPD. Infants with birth weight 501g to 1000g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide \[PCO(2)\] target \>52 mm Hg) or routine ventilation (PCO(2) target \<48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. The trial was terminated by the Steering Committee when the interim analysis for the Data Safety and Monitoring Committee showed a higher rate of spontaneous gastrointestinal perforations in the dexamethasone-treated infants. Neurodevelopment was assessed at 18-22 months postmenstrual age.
Interventions
PROCEDUREMinimal mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target (\>52 mm Hg)
PROCEDURERoutine mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target \<48 mm Hg)
DRUGDexamethasone
Treatment with the study medication was initiated within 24 hours after birth. The dexamethasone-treated infants received a 10-day tapered course (0.15 mg of dexamethasone per kilogram per day for three days, followed by 0.10 mg per kilogram for three days, 0.05 mg per kilogram for two days, and 0.02 mg per kilogram for two days), with the daily dose divided in half and given at 12-hour intervals intravenously or orally, if an intravenous catheter was no longer in place.
DRUGPlacebo
The infants in the placebo groups received equal volumes of saline.
Sponsors
National Center for Research Resources (NCRR)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Minutes to 10 Days
Healthy volunteers
No
Inclusion criteria
* Greater than 12 hrs of age and less than 10 days chronologic age * 501-1000 gm * Intubated and mechanically ventilated before 12 hrs * Indwelling vascular catheter * Infants 751-100 gm must be receiving FiO2 greater than 0.30 and have received at least 1 dose of surfactant at randomization * Parental consent
Exclusion criteria
* Major congenital anomaly * Symptomatic non-bacterial infection * Permanent neuromuscular conditions that affect respiration * Terminal illness (defined as pH values less than 6.8 for more than 2 hours or persistent bradycardia associated with hypoxia for more than 2 hours) * Use of postnatal corticosteroids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Death or moderate to severe bronchopulmonary dysplasia | 36 weeks postmenstrual age |
Secondary
| Measure | Time frame |
|---|---|
| Mechanical ventilation | 36 weeks postmenstrual age |
| Pulmonary interstitial emphysema | 36 weeks postmenstrual age |
| Pneumothorax | 36 weeks postmenstrual age |
| Open-label steroids | 36 weeks postmenstrual age |
| Reintubation | 36 weeks postmenstrual age |
| Intracranial hemorrhage (IVH) III or IV | 36 weeks postmenstrual age |
| Periventricular leukomalacia | 36 weeks postmenstrual age |
| Necrotizing enterocolitis | 36 weeks postmenstrual age |
| Duration of oxygen supplementation | 36 weeks postmenstrual age |
| Death | 36 weeks postmenstrual age |
| Length of hospitalization | Hospital discharge |
| Death or neurodevelopmental impairment | 18-22 months corrected age |
| Neurodevelopmental impairment | 18-22 months corrected age |
| Cerebral palsy | 18-22 months corrected age |
| Bilateral blindness | 18-22 months corrected age |
| Deafness | 18-22 months corrected age |
| Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI) | 18-22 months corrected age |
| Rehospitalizations | 18-22 months corrected age |
| Duration of ventilation | 36 weeks postmenstrual age |
Countries
United States
Outcome results
None listed