Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 21;19(1):363.
doi: 10.1186/s12887-019-1735-9.

Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants - study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy

Christian A Maiwald  1   2 , Hendrik J Niemarkt  3 , Christian F Poets  1 , Michael S Urschitz  4 , Jochem König  4 , Helmut Hummler  5 , Dirk Bassler  6 , Corinna Engel  2 , Axel R Franz  7   8 ; FiO2-C Study Group
Collaborators, Affiliations

Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants - study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy

Christian A Maiwald et al. BMC Pediatr. .

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 (FiO2-C) reduces time outside the hemoglobin oxygen saturation (SpO2) 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 FiO2-C (in addition to routine manual control (RMC) of FiO2), 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 FiO2-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks). FiO2-C is provided by commercially available and CE-marked ventilators with an FiO2-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 FiO2-C showed improved time ELGANs spent within their assigned SpO2 target range, but effects of FiO2-C on clinical outcomes are yet unknown and will be addressed in the FiO2-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO2-C may be implemented as standard therapy.

Trial registration: The study is registered at www.ClinicalTrials.gov: NCT03168516 , May 30, 2017.

Keywords: Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C); Infant, premature; Intermittent hypoxemia and hyperoxemia; Oxygen.

PubMed Disclaimer

Conflict of interest statement

C.F. Poets received speaker honoraria from Masimo Inc. and Sentec. All other contributors declare that they do not have competing interest.

Figures

Fig. 1
Fig. 1
Anticipated Trial Flow
See this image and copyright information in PMC

References

    1. Di Fiore JM, Martin RJ, Gauda EB. Apnea of prematurity--perfect storm. Resp Physiol Neurobi. 2013;189(2):213–222. doi: 10.1016/j.resp.2013.05.026. - DOI - PubMed
    1. Martin RJ, Di Fiore JM, Macfarlane PM, Wilson CG. Physiologic basis for intermittent hypoxic episodes in preterm infants. Adv Exp Med Biol. 2012;758:351–358. doi: 10.1007/978-94-007-4584-1_47. - DOI - PubMed
    1. Bolivar JM, Gerhardt T, Gonzalez A, Hummler H, Claure N, Everett R, et al. Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation. J Pediatr. 1995;127(5):767–773. doi: 10.1016/S0022-3476(95)70171-0. - DOI - PubMed
    1. Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, et al. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010;157(1):69–73. doi: 10.1016/j.jpeds.2010.01.046. - DOI - PMC - PubMed
    1. Di Fiore JM, Kaffashi F, Loparo K, Sattar A, Schluchter M, Foglyano R, et al. The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants. Pediatr Res. 2012;72(6):606–612. doi: 10.1038/pr.2012.132. - DOI - PMC - PubMed

Publication types

Associated data