Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial

Kevin P Seitz¹, Bradley D Lloyd¹, Li Wang¹, Matthew S Shotwell¹, Edward T Qian¹, Roger K Richardson¹, Jeffery C Rooks¹, Vanessa Hennings-Williams¹, Claire E Sandoval¹, Whitney D Richardson¹, Tracy Morgan¹, Amber N Thompson¹, Pamela G Hastings¹, Terry P Ring¹, Joanna L Stollings¹, Erica M Talbot¹, David J Krasinski¹, Bailey Decoursey¹, Kevin W Gibbs¹, Wesley H Self¹, Amanda S Mixon¹, Todd W Rice¹, Matthew W Semler¹, Jonathan D Casey¹

Affiliations

Affiliation

¹ Department of Medicine (K. P. S., E. T. Q., T. W. R., M. W. S., and J. D. C.), Division of Allergy, Pulmonary and Critical Care Medicine; the Department of Emergency Medicine (B. D. L. and W. H. S.); the Department of Biostatistics (L. W. and M. S. S.); the Department of Respiratory Care (R. K. R., J. C. R., V. H.-W., C. E. S., W. D. R., T. M., A. N. T., P. G. H., and T. P. R.); the Department of Pharmaceutical Services (J. L. S.); the Department of Medicine (E. M. T., D. J. K., and B. D.), Vanderbilt University Medical Center, Nashville, TN; the Section on Pulmonary, Critical Care, Allergy, and Immunology (K. W. G.), Wake Forest School of Medicine, Winston-Salem, NC; the Vanderbilt Institute for Clinical and Translational Research (W. H. S.), Vanderbilt University Medical Center, Nashville, TN; the Department of Medicine, Division of General Internal Medicine and Public Health (A. S. M.), Vanderbilt University Medical Center, Nashville, TN; and the VA Tennessee Valley Healthcare System, Geriatric Research, Education, and Clinical Center (A. S. M.), Nashville, TN.

PMID: 38742219
PMCID: PMC11090486
DOI: 10.1016/j.chstcc.2023.100033

Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial

Kevin P Seitz et al. CHEST Crit Care. 2024 Mar.

. 2024 Mar;2(1):100033.

doi: 10.1016/j.chstcc.2023.100033. Epub 2023 Nov 25.

Authors

Affiliation

¹ Department of Medicine (K. P. S., E. T. Q., T. W. R., M. W. S., and J. D. C.), Division of Allergy, Pulmonary and Critical Care Medicine; the Department of Emergency Medicine (B. D. L. and W. H. S.); the Department of Biostatistics (L. W. and M. S. S.); the Department of Respiratory Care (R. K. R., J. C. R., V. H.-W., C. E. S., W. D. R., T. M., A. N. T., P. G. H., and T. P. R.); the Department of Pharmaceutical Services (J. L. S.); the Department of Medicine (E. M. T., D. J. K., and B. D.), Vanderbilt University Medical Center, Nashville, TN; the Section on Pulmonary, Critical Care, Allergy, and Immunology (K. W. G.), Wake Forest School of Medicine, Winston-Salem, NC; the Vanderbilt Institute for Clinical and Translational Research (W. H. S.), Vanderbilt University Medical Center, Nashville, TN; the Department of Medicine, Division of General Internal Medicine and Public Health (A. S. M.), Vanderbilt University Medical Center, Nashville, TN; and the VA Tennessee Valley Healthcare System, Geriatric Research, Education, and Clinical Center (A. S. M.), Nashville, TN.

PMID: 38742219
PMCID: PMC11090486
DOI: 10.1016/j.chstcc.2023.100033

Abstract

Background: 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.

Research question: 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?

Study design and methods: 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.

Results: 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.

Interpretation: Prespecifying the full statistical analysis plan prior to completion of enrollment increases rigor, reproducibility, and transparency of the trial results.

Clinical trial registration: The trial was registered with clinicaltrials.gov on October 3, 2022, before initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).

Keywords: artificial respiration; critical illness; feasibility studies; respiratory failure.

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Figures

**Figure 1 –**
Group assignment during the MODE trial. For each of the 1-month study periods, the study unit is randomly assigned to a study mode for continuous mandatory ventilation. The letters ‘A,’ ‘B,’ and ‘C’ each correspond to one of the three study modes.

See this image and copyright information in PMC

Update of

Protocol and statistical analysis plan for the Mode of Ventilation During Critical IllnEss (MODE) trial.
Seitz KP, Lloyd BD, Wang L, Shotwell MS, Qian ET, Richardson RK, Rooks JC, Hennings-Williams V, Sandoval CE, Richardson WD, Morgan T, Thompson AN, Hastings PG, Ring TP, Stollings JL, Talbot EM, Krasinski DJ, Decoursey B, Gibbs KW, Self WH, Mixon AS, Rice TW, Semler MW, Casey JD. Seitz KP, et al. medRxiv [Preprint]. 2023 Jul 24:2023.07.21.23292998. doi: 10.1101/2023.07.21.23292998. medRxiv. 2023. Update in: CHEST Crit Care. 2024 Mar;2(1):100033. doi: 10.1016/j.chstcc.2023.100033. PMID: 37546787 Free PMC article. Updated. Preprint.

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Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial

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Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial

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