RESUMO
OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.
Assuntos
Doenças do Prematuro , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Insuficiência Respiratória , Produtos Biológicos , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Recém-Nascido , Doenças do Prematuro/epidemiologia , Fosfolipídeos , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Insuficiência Respiratória/tratamento farmacológico , Tensoativos/uso terapêuticoRESUMO
OBJECTIVES: To investigate, in infants born preterm with or without bronchopulmonary dysplasia (BPD), the trajectory of tidal breathing flow-volume (TBFV) parameters in the first 2 years of life; the association between TBFV parameters and perinatal risk factors; and the predictive value of TBFV parameters for rehospitalizations due to respiratory infections and wheeze. STUDY DESIGN: We retrospectively analyzed TBFV measurements performed at 0-6, 6-12, and 12-24 months of corrected age in 97 infants <32 weeks of gestation and <1500 g. We assessed the association between TBFV parameters and perinatal risk-factors using linear regressions and the predictive capacity for subsequent respiratory morbidity using logistic regressions. We used the area under the curve and likelihood ratio test (LRT) to compare nested models. RESULTS: Time to peak tidal expiratory flow/expiratory time ratio (tPTEF/tE) was lower than normal for the first 2 years of corrected age. Longer duration of oxygen supplementation, intubation, and respiratory support were associated with reduced tPTEF/tE at all time points. For each z-score increase in tPTEF/tE, the OR for rehospitalizations decreased by 0.70. tPTEF/tE added significantly to BPD classifications alone in predicting rehospitalizations (area under the receiver operating characteristic curve = 0.81 vs 0.76, P value for LRT = .0012), and wheeze (area under the receiver operating characteristic curve = 0.76 vs 0.71, P value for LRT <.001). CONCLUSIONS: Infants born preterm, with and without BPD, display persistent airway obstruction during the first 2 years of life. tPTEF/tE may identify infants at greater risk of severe respiratory morbidity.