Investigators from multiple institutions conducted a blinded randomized controlled trial to assess the effectiveness of intra-tracheal administration of surfactant via a thin catheter (minimally invasive surfactant treatment [MIST]) in premature infants treated with continuous positive airway pressure (CPAP) for respiratory distress syndrome. Participants were neonates born at 25-28 weeks’ gestation, treated with CPAP of 5-8 cm H2O and requiring a FiO2 of ≥0.30, and who were receiving care at 1 of 33 NICUs in 11 countries between 2011 and 2020. Study infants were randomized to MIST or a sham treatment (control) group; those in the MIST group received surfactant (200 mg/kg of poractant alfa) intratracheally via a 16-gauge catheter. The primary outcome was a composite of death or development of bronchopulmonary dysplasia (BPD) by 36 weeks postmenstrual age. Infants who were receiving mechanical ventilation, CPAP, or high-flow nasal cannula therapy, or required supplemental oxygen at an FiO2 of ≥0.30, or did not pass a room air test at 36 weeks post-menstrual age, were classified as having BPD. The main secondary outcomes were individual measures for death and BPD. There were multiple other secondary outcomes, including need for intubation within 72 hours of birth, pneumothorax, and development of patent ductus arteriosus (PDA). Generalized linear models were used to compare outcomes among neonates in the MIST and control groups, with gestational age included in the model. The investigators planned to enroll 606 participants in the study, but enrollment was discontinued in March 2020 due to the COVID-19 pandemic.
A total of 488 neonates were enrolled in the study, and 485 were included in the primary analysis. The median gestational age of participants was 27.3 weeks; 241 were randomized to MIST and 244 to the control group. The primary outcome of death or BPD at 36 weeks postmenstrual age occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) of those randomized to the control group (risk reduction [RR], 0.87; 95% CI, 0.74, 1.03; P = 0.10). Among those randomized to MIST, 24 (10%) died prior to 36 weeks postmenstrual age compared to 19 (7.8%) of controls (RR, 1.27; 95% CI, 0.63, 2.57; P = 0.51). However, the rate of BPD was significantly lower in infants treated with MIST than controls (rates 37.3% and 45.3%, respectively; RR, 0.83; 95% CI, 0.70, 0.98; P = 0.03). The need for intubation by 72 hours, rate of pneumothorax, and incidence of PDA all were significantly lower among infants in the MIST group than in control infants.
The authors conclude that MIST treatment was not associated with a decreased risk of death or BPD by 36 weeks postmenstrual age as a composite measure in premature...