Statistical analysis plan for the FiO2-C trial: effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcomes of extremely preterm infants-a randomized-controlled parallel group multicentre trial for safety and efficacy.
Jochem König, Anette Stauch, Corinna Engel, Michael S Urschitz, Axel R Franz
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引用次数: 0
Abstract
Background: Extremely low gestational age neonates (ELGANs, i.e. those born before 28 weeks postmenstrual age (PMA)) often require supplemental oxygen and frequently experience intermittent hypo- and hyperoxemic episodes. Exposure to episodes with inadequate oxygen concentrations has been shown to be associated with an increased risk of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI) and death. Closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) reduces number and duration of hypo- and hyperoxemic episodes in ELGANs. Its impacts on clinically important short- and long-term outcomes such as ROP, BPD, NEC, NDI and mortality have not yet been studied.
Methods: An outcome-assessor-blinded, multicentre, randomized-controlled, parallel-group trial for superiority was designed to study the effects of FiO2-C (provided by standard infant ventilators) in addition to routine manual control (RMC) during respiratory support, compared to RMC only, on short- and long-term clinical outcomes in ELGANs. Two co-primary composite outcomes were defined: (i) death, severe ROP, BPD or NEC, assessed at 36 weeks PMA or, in case of ROP, until complete vascularization of the retina; (ii) death or NDI (defined as language/cognitive delay, motor impairment, severe visual impairment or hearing impairment), assessed at 2 years corrected age.
Results: Primary outcomes will be compared between the two intervention groups using a Cochran-Mantel-Haenszel test. The factors considered for randomization (centre, sex and gestational age at birth (< 26 weeks and ≥ 26 weeks)) will be used to define strata. Results will be presented as adjusted odds ratios with two-sided 95% and 97.5% confidence intervals and two-sided p values.
Conclusions: The statistical analyses for the FiO2-C trial were defined in the study protocol and specified in detail in this statistical analysis plan published prior to any statistical analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.
Trial registration: ClinicalTrials.gov NCT03168516. Registered on May 30, 2017.
期刊介绍：
Trials is an open access, peer-reviewed, online journal that will encompass all aspects of the performance and findings of randomized controlled trials. Trials will experiment with, and then refine, innovative approaches to improving communication about trials. We are keen to move beyond publishing traditional trial results articles (although these will be included). We believe this represents an exciting opportunity to advance the science and reporting of trials. Prior to 2006, Trials was published as Current Controlled Trials in Cardiovascular Medicine (CCTCVM). All published CCTCVM articles are available via the Trials website and citations to CCTCVM article URLs will continue to be supported.
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