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 (CLAC_fast, ≤2 FiO₂ adjustments/min), compared with routine manual control (RMC_only), 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 (CLAC_slow: ≤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 CLAC_fast was compared with RMC_only and RMC supported by CLAC_slow. 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 CLAC_fast versus 65%±11% [61% to 68%] for CLAC_slow versus 58%±11% [55% to 62%] for RMC_only. Prespecified hypothesis tests of: (A) superiority of CLAC_fast versus RMC_only and (B) non-inferiority of CLAC_fast versus CLAC_slow 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.