Sustained lung inflation does not decrease bronchopulmonary dysplasia or death among extremely preterm infants: A Commentary on The SAIL randomised clinical trial.

Abstract

The CONSORT guidelines allow for meaningful assessment of how randomised controlled trials have been designed, analysed and reported, and a thorough evaluation of a RCT within the context of these guidelines allows for fair interpretation of the data presented.1 Title and abstract sections of the article identifies the trial as a randomised trial and includes a structured summary of trial design, method, result and conclusion.2 The introduction section includes the scientific background, rationale as well as specific objectives of whether sustained lung inflation at birth reduces bronchopulmonary dysplasia (BPD) or death which is a relevant topic as the rates of BPD remain high.3 Method section describes the trial design (parallel-group trial with permuted block randomisation), eligibility criteria, settings and locations of participants. There were no critical changes in the method after starting the trial. Interventions to each group and outcomes, both primary and secondary, were defined in sufficient detail. The sample size was calculated to detect absolute risk reduction of death or BPD by 12.5% with 80% power and 2-sided α = 0.038 (adjusted P-value for two planned interim analyses). The authors had pre-specified planned interim analysis and stopping rules. Computer-generated parallel-group randomisation was done, and the trial was not blinded. Statistical analysis, for primary and secondary analyses, as well as subgroup analyses and sensitivity analyses were robust. Flow diagram accounting for all enrolled infants was presented. The investigators planned to recruit 600 infants but trial was stopped early after recruiting 426 infants as predefined secondary safety endpoint was met when the data and safety monitoring committee reported suggestion of higher death in the sustained inflation group within the first 48 hours of life compared to control group (7.4% vs 1.4% aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Baseline characteristics of the two groups were comparable. Primary outcomes death or BPD at 36 weeks, as well as death and BPD at 36 weeks, were not different between the groups. There were no significant differences in secondary outcomes. The discussion section mentions the limitations of the article. The article does not report the comparative outcomes between the centres where sustained lung inflation was routine versus the centres where the procedure was investigational. These findings would be meaningful because the familiarity of the procedure may change the outcomes. The trial is registered in clinicaltrials.gov, the full protocol is available, and funding information is provided. Previous trials to evaluate the efficacy and effectiveness of sustained lung inflation on preterm infants that enrolled preterm infants of different gestational age and birth weight have shown the inconsistent result in short-term outcomes.4-6 Animal studies have shown an inverse relationship between gestational age and lung aeration from sustained lung inflation,7 so the response to sustained inflation may vary with the size and gestational age of an infant. The SAIL trial performed well under CONSORT assessment and concluded that sustained lung inflation should not be used in this patient population. https://ebneo.org/2019/07/sustained-lung-inflation-bpd/ None.