Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE)
| Autor: | Mark L. Hudak, Joseph E. Rower, Cheryl J. Chapin, Robert M. Ward, Philip L. Ballard, Roberta A. Ballard, Jeanette M. Asselin, Cindy T. McEvoy, Joern Hendrik Weitkamp, Rajan Wadhawan, Julia Harris |
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| Rok vydání: | 2020 |
| Předmět: |
Budesonide
Male Risk medicine.medical_specialty Hydrocortisone medicine.medical_treatment Birth weight Anti-Inflammatory Agents Gastroenterology Pediatrics Paediatrics and Reproductive Medicine 03 medical and health sciences Surface-Active Agents 0302 clinical medicine 030225 pediatrics Internal medicine medicine Intubation Birth Weight Humans Dosing Respiratory system Bronchopulmonary Dysplasia Mechanical ventilation Clinical Research Article Dose-Response Relationship Drug business.industry Infant Newborn Gestational age medicine.disease Treatment Outcome Bronchopulmonary dysplasia Infant Extremely Premature Pediatrics Perinatology and Child Health Public Health and Health Services Cytokines Female business 030217 neurology & neurosurgery Infant Premature medicine.drug |
| Zdroj: | Pediatric research, vol 88, iss 4 Pediatric Research |
| Popis: | Background Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. Methods Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3−14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). Results Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. Conclusions Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action. |
| Databáze: | OpenAIRE |
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