biostudies-literatureSeitz KPNational Center for Advancing Translational SciencesNCATS NIH HHSNCRR NIH HHSNational Heart, Lung, and Blood InstituteNHLBI NIH HHSNational Institutes of Health100033https://www.ebi.ac.uk/biostudies/studies/S-EPMC11090486biostudies-literatureUnknown2(1)<h4>Background</h4>For every critically ill adult receiving invasive mechanical ventilation, clinicians must select a mode of ventilation. The mode of ventilation determines whether the ventilator directly controls the tidal volume or the inspiratory pressure. Newer hybrid modes allow clinicians to set a target tidal volume; the ventilator controls and adjusts the inspiratory pressure. A strategy of low tidal volumes and low plateau pressure improves outcomes, but the optimal mode to achieve these targets is not known.<h4>Research question</h4>Can a cluster-randomized trial design be used to assess whether the mode of mandatory ventilation affects the number of days alive and free of invasive mechanical ventilation among critically ill adults?<h4>Study design and methods</h4>The Mode of Ventilation During Critical Illness (MODE) trial is a cluster-randomized, multiple-crossover pilot trial being conducted in the medical ICU at an academic center. The MODE trial compares the use of volume control, pressure control, and adaptive pressure control. The study ICU is assigned to a single-ventilator mode (volume control vs pressure control vs adaptive pressure control) for continuous mandatory ventilation during each 1-month study block. The assigned mode switches every month in a randomly generated sequence. The primary outcome is ventilator-free days to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of mechanical ventilation to 28 days after enrollment. Enrollment began November 1, 2022, and will end on July 31, 2023.<h4>Results</h4>This manuscript describes the protocol and statistical analysis plan for the MODE trial of ventilator modes comparing volume control, pressure control, and adaptive pressure control.<h4>Interpretation</h4>Prespecifying the full statistical analysis plan prior to completion of enrollment increases rigor, reproducibility, and transparency of the trial results.<h4>Clinical trial registration</h4>The trial was registered with clinicaltrials.gov on October 3, 2022, before initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).CHEST critical careProtocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial.PMC11090486UL1 TR002243U01 HL168478T32HL087738UL1TR002243U24 TR004437K23 HL153584K23 HL143053U24 TR 001608U24 TR001608K23HL143053UL1 RR024975UL1 RR 024975K23HL153584T32 HL0877381U24TR004437Hennings-Williams VSandoval CEHastings PGQian ETRing TPDecoursey BRice TWRooks JCMixon ASThompson ANShotwell MSGibbs KWWang LStollings JLSemler MWLloyd BDTalbot EMRichardson RKSeitz KPMorgan TRichardson WDSelf WHKrasinski DJCasey JDfalseProtocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial.<h4>Background</h4>For every critically ill adult receiving invasive mechanical ventilation, clinicians must select a mode of ventilation. The mode of ventilation determines whether the ventilator directly controls the tidal volume or the inspiratory pressure. Newer hybrid modes allow clinicians to set a target tidal volume; the ventilator controls and adjusts the inspiratory pressure. A strategy of low tidal volumes and low plateau pressure improves outcomes, but the optimal mode to achieve these targets is not known.<h4>Research question</h4>Can a cluster-randomized trial design be used to assess whether the mode of mandatory ventilation affects the number of days alive and free of invasive mechanical ventilation among critically ill adults?<h4>Study design and methods</h4>The Mode of Ventilation During Critical Illness (MODE) trial is a cluster-randomized, multiple-crossover pilot trial being conducted in the medical ICU at an academic center. The MODE trial compares the use of volume control, pressure control, and adaptive pressure control. The study ICU is assigned to a single-ventilator mode (volume control vs pressure control vs adaptive pressure control) for continuous mandatory ventilation during each 1-month study block. The assigned mode switches every month in a randomly generated sequence. The primary outcome is ventilator-free days to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of mechanical ventilation to 28 days after enrollment. Enrollment began November 1, 2022, and will end on July 31, 2023.<h4>Results</h4>This manuscript describes the protocol and statistical analysis plan for the MODE trial of ventilator modes comparing volume control, pressure control, and adaptive pressure control.<h4>Interpretation</h4>Prespecifying the full statistical analysis plan prior to completion of enrollment increases rigor, reproducibility, and transparency of the trial results.<h4>Clinical trial registration</h4>The trial was registered with clinicaltrials.gov on October 3, 2022, before initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).2024-01-01T00:00:00Z2024 Mar2026-06-03T04:32:05.119Z2026-04-24T03:09:54.567ZS-EPMC110904863874221910.1016/j.chstcc.2023.100033