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Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO$_{2}$-C) on outcome of extremely preterm infants - study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy


Maiwald, Christian A; Niemarkt, Hendrik J; Poets, Christian F; Urschitz, Michael S; König, Jochem; Hummler, Helmut; Bassler, Dirk; Engel, Corinna; Franz, Axel R; FiO2-C Study Group (2019). Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO$_{2}$-C) on outcome of extremely preterm infants - study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy. BMC Pediatrics, 19:363.

Abstract

BACKGROUND Most extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA. Closed-loop automated control of the inspiratory fraction of oxygen (FiO$_{2}$-C) reduces time outside the hemoglobin oxygen saturation (SpO$_{2}$) target range, number and duration of hypo- and hyperoxemic episodes and caregivers' workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.
METHODS An outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO$_{2}$-C (in addition to routine manual control (RMC) of FiO$_{2}$), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO$_{2}$-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks). FiO$_{2}$-C is provided by commercially available and CE-marked ventilators with an FiO$_{2}$-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.
DISCUSSION Short-term studies on FiO$_{2}$-C showed improved time ELGANs spent within their assigned SpO$_{2}$ target range, but effects of FiO$_{2}$-C on clinical outcomes are yet unknown and will be addressed in the FiO$_{2}$-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO$_{2}$-C may be implemented as standard therapy.

Abstract

BACKGROUND Most extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA. Closed-loop automated control of the inspiratory fraction of oxygen (FiO$_{2}$-C) reduces time outside the hemoglobin oxygen saturation (SpO$_{2}$) target range, number and duration of hypo- and hyperoxemic episodes and caregivers' workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.
METHODS An outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO$_{2}$-C (in addition to routine manual control (RMC) of FiO$_{2}$), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO$_{2}$-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks). FiO$_{2}$-C is provided by commercially available and CE-marked ventilators with an FiO$_{2}$-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.
DISCUSSION Short-term studies on FiO$_{2}$-C showed improved time ELGANs spent within their assigned SpO$_{2}$ target range, but effects of FiO$_{2}$-C on clinical outcomes are yet unknown and will be addressed in the FiO$_{2}$-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO$_{2}$-C may be implemented as standard therapy.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neonatology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pediatrics, Perinatology and Child Health
Language:English
Date:21 October 2019
Deposited On:10 Dec 2019 14:00
Last Modified:12 Sep 2020 13:11
Publisher:BioMed Central
ISSN:1471-2431
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12887-019-1735-9
PubMed ID:31630690

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