Objective Closed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO2) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLACfast, ≤2 FiO2 adjustments/min), compared with routine manual control (RMConly), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLACslow: ≤0.3 FiO2 adjustments/min).
Design Unblinded randomised controlled crossover study comparing three modes of FiO2 control in random order for 8 hours each: RMC supported by CLACfast was compared with RMConly and RMC supported by CLACslow. A computer-generated list of random numbers using a block size of six was used for the allocation sequence.
Setting Two German tertiary university neonatal intensive care units.
Patients Of 23 randomised patients, 19 were analysed (mean±SD gestational age 27±2 weeks; age at randomisation 24±10 days) on non-invasive (n=18) or invasive (n=1) respiratory support at FiO2 >0.21.
Main outcome measure Target%.
Results Mean±SD [95% CI] Target% was 68%±11% [65% to 71%] for CLACfast versus 65%±11% [61% to 68%] for CLACslow versus 58%±11% [55% to 62%] for RMConly. Prespecified hypothesis tests of: (A) superiority of CLACfast versus RMConly and (B) non-inferiority of CLACfast versus CLACslow with margin of 5% yielded one-sided p values of <0.001 for both comparisons.
Conclusions This revised and faster CLAC algorithm was still superior to routine care in infants on respiratory support and not inferior to a previously tested slower algorithm.
Trial registration number NCT03163108.
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CES and AK contributed equally.
Contributors CES coordinated and supervised patient recruitment and data collection at the study centres, evaluated the analyses and drafted the initial and the revised manuscript; AK conducted patient recruitment and data collection, evaluated the analyses and reviewed the revised manuscript; NSB conducted patient recruitment and data collection and critically reviewed the manuscript; AF was involved in study design, supervised patient recruitment and data collection, evaluated the analyses and critically reviewed the manuscript; JK carried out the statistical analyses and critically reviewed and revised the manuscript; EM and CFP supervised the study design and critically reviewed the manuscript; AS designed and developed the closed-loop automatic control (CLAC) algorithm, analysed the biosignal data and critically reviewed the manuscript; MSU led the study team, received the research grant, conceptualised and designed the study, supervised the biosignal and statistical analyses and revised the draft of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding This study was supported by a research grant from Löwenstein Medical (Bad Ems; Germany), which also provided two ventilators. The granting company had no impact on the study design, data acquisition and analysis and writing of the manuscript.
Competing interests The University of Tuebingen holds a patent on the CLAC algorithm for automated oxygen control and have a licencing agreement with Löwenstein Medical in relation to this algorithm. AF and CFP are supported by a grant of the German Ministry of Research and Education for conducting the FiO2 Controller study on medium-term effects of CLAC of FiO2. CES, AF and CFP also received a research grant from Fritz Stephan GmbH. CFP received speaker honoraria from Masimo Inc.
Patient consent for publication Not required.
Ethics approval Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen 470/2016BO1 and Ethikkommission der Landesärztekammer Rheinland Pfalz 837.126.17 .
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement Data are available on reasonable request.
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