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Landmark trials in critical care have demonstrated that, among critically ill adults receiving invasive mechanical ventilation, the use of low tidal volumes and low airway pressures prevents lung injury and improves patient outcomes. Limited evidence, however, informs the best method of mechanical ventilation to achieve these targets. To provide mechanical ventilation, clinicians must choose between modes of ventilation that directly control tidal volumes ("volume control"), modes that directly control the inspiratory airway pressure ("pressure control"), and modes that are hybrids ("adaptive pressure control"). Whether the choice of the mode used to target low tidal volumes and low inspiratory plateau pressures affects clinical outcomes for critically ill adults receiving mechanical ventilation is unknown. All three modes of mechanical ventilation are commonly used in clinical practice. A large, multicenter randomized trial comparing available modes of mechanical ventilation is needed to understand the effect of each mode on clinical outcomes. The investigators propose a 9-month cluster-randomized cluster-crossover pilot trial evaluating the feasibility of comparing three modes (volume control, pressure control, and adaptive pressure control) for mechanically ventilated ICU patients with regard to the outcome of days alive and free of invasive mechanical ventilation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Volume Control mode | Active Comparator | During invasive mechanical ventilation in a study location, Volume Control will be used as the mode for continuous mandatory ventilation. |
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| Pressure Control mode | Active Comparator | During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation. |
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| Adaptive Pressure Control mode | Active Comparator | During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Volume Control mode | Other | Volume Control mode for mechanical ventilation |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Ventilator-free Days (VFDs) to Day 28 After Enrollment | Number of days alive and free from invasive mechanical ventilation between the final liberation from invasive mechanical ventilation before 28 days and study day 28. Patients who continue to receive invasive mechanical ventilation at day 28 or have died prior to day 28 will receive zero VFDs. For patients who return to invasive mechanical ventilation and are subsequently liberated from invasive mechanical ventilation prior to day 28, VFDs will be counted from final liberation from mechanical ventilation. | Enrollment to 28 days |
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| Measure | Description | Time Frame |
|---|---|---|
| Exposure to Assigned Study Mode in First 3 Days (Feasibility Outcome) | Percentage of time in the assigned mode while receiving invasive mechanical ventilation in the study ICU between enrollment and 72 hours after enrollment. | Enrollment to 72 hours |
| Adherence to Study Mode in First 3 Days (Feasibility Outcome) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kevin P. Seitz, MD, MSc | Clinical Fellow | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40189043 | Derived | Seitz KP, Lloyd BD, Wang L, Shotwell MS, Qian ET, Muhs AL, Richardson RK, Rooks JC, Hennings-Williams V, Sandoval CE, Richardson WD, Morgan TL, Thompson AN, Hastings PG, Ring TP, Stollings JL, Talbot EM, Krasinski DJ, DeCoursey BR, Marvi TK, DeMasi SC, Gibbs KW, Self WH, Mixon AS, Rice TW, Semler MW, Casey JD; Pragmatic Critical Care Research Group. Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial. Chest. 2025 Oct;168(4):912-923. doi: 10.1016/j.chest.2025.03.024. Epub 2025 Apr 4. | |
| 38742219 |
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Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.
The data will become available 3 months following publication of primary trial results and will remain available for at least 5 years.
Following publication, individual patient data will be made available for sharing to researchers with 1) a signed data access agreement, 2) research testing a hypothesis, 3) a protocol that has been approved by an institutional review board, and 4) a proposal that has received approval from the principal investigator.
Even though the final dataset will be stripped of identifiers prior to release for sharing, the inherent link between the period in which the patient was admitted to the study ICU and group assignment in a cluster-crossover trial introduces a significant risk for deductive disclosure of subjects. Thus, we will make the data available to users only under a data sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
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Patients will be assigned to only the mode of ventilation at enrollment and analyzed according to the assigned mode. If patients continue to receive mechanical ventilation at the start of the next study block, choice of the ventilator mode will be at the discretion of clinicians. Patients will not crossover to another mode of ventilation. Participation ends at the first of hospital discharge or death.
During the 9 months of enrollment in the MODE trial, the entire medical ICU will be assigned to a single ventilator mode with the assigned mode alternating between volume control, pressure control, and adaptive pressure control modes every month in a randomly generated sequence. All patients who receive invasive mechanical ventilation and meet inclusion criteria without meeting exclusion criteria will be enrolled. The study mode will be assigned according to the month of enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Volume Control Mode | During invasive mechanical ventilation in a study location, Volume Control will be used as the mode for continuous mandatory ventilation. |
| FG001 | Pressure Control Mode | During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation. |
| FG002 | Adaptive Pressure Control Mode | During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Volume Control Mode | During invasive mechanical ventilation in a study location, Volume Control will be used as the mode for continuous mandatory ventilation. |
| BG001 | Pressure Control Mode |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ventilator-free Days (VFDs) to Day 28 After Enrollment | Number of days alive and free from invasive mechanical ventilation between the final liberation from invasive mechanical ventilation before 28 days and study day 28. Patients who continue to receive invasive mechanical ventilation at day 28 or have died prior to day 28 will receive zero VFDs. For patients who return to invasive mechanical ventilation and are subsequently liberated from invasive mechanical ventilation prior to day 28, VFDs will be counted from final liberation from mechanical ventilation. | Posted | Median | Inter-Quartile Range | Ventilator-free days to day 28 | Enrollment to 28 days |
|
from enrollment until end of follow-up, up to 28 days or hospital discharge
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Volume Control Mode | During invasive mechanical ventilation in a study location, Volume Control will be used as the mode for continuous mandatory ventilation. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kevin P Seitz, MD | Vanderbilt University Medical Center | 615-936-9329 | kevin.seitz@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 21, 2023 | Nov 13, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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In the MODE trial, the entire study ICU will be assigned to a single mode for continuous mandatory ventilation and the ICU will switch between volume control, pressure control, and adaptive pressure control every month in a randomly generated sequence (cluster-crossover).
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Observer bias will be minimized by use of objective endpoints collected in duplicate by [1] study personnel blinded to group assignment and [2] automated data extraction from the electronic health record.
| Pressure Control mode |
| Other |
Pressure Control mode for mechanical ventilation |
|
| Adaptive Pressure Control mode | Other | Adaptive Pressure Control mode for mechanical ventilation |
|
Percentage of time in the assigned mode while receiving invasive mechanical ventilation in the study ICU with a mandatory mode between enrollment and 72 hours after enrollment (excluding time spent in spontaneous modes). |
| Enrollment to 72 hours |
| Time From Enrollment to Initiation of Assigned Mode of Mechanical Ventilation (Feasibility Outcome) | Enrollment to 28 days |
| Number of Patients With a "Mode Modification Sheet" Completed by Treating Clinicians (Feasibility Outcome) | Enrollment to 28 days |
| Exhaled Tidal Volume (mL/kg Predicted Body Weight) (Exploratory Efficacy and Safety Outcome) | Enrollment to the first of extubation, 28 days, or death |
| Percentage of Exhaled Tidal Volumes Above Target Range (Exploratory Efficacy and Safety Outcome) | Percentage of exhaled tidal volume values above target range (>8mL/kg predicted body weight), reported as a percentage. | Enrollment to the first of extubation, 28 days, or death |
| Hypoxemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) | Hypoxemia during mechanical ventilation defined as an SpO2 <85% for more than 5 minutes | Enrollment to the first of 28 days or death |
| Severe Acidemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) | Severe acidemia during mechanical ventilation: pH < 7.1 on blood gas | Enrollment to 28 days |
| Number of Blood Gas Laboratory Tests on the First Study Day (Exploratory Safety and Efficacy Outcome) | Enrollment to 1 day |
| Pneumomediastinum or Pneumothorax During Mechanical Ventilation (Exploratory Efficacy and Safety Outcome) | Enrollment to 28 days |
| SOFA Score on the First Study Day (Exploratory Safety and Efficacy Outcome) | The Sequential Organ Failure Assessment (SOFA) score is composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction or failure. Scores range from 0 (no evidence of organ dysfunction or failure) to 24 (evidence of severe organ dysfunction or failure). The mean of SOFA scores on study day 1 was calculated for each patient. | Enrollment to 1 day |
| Delirium and Coma Free Days to Day 28 (Exploratory Efficacy and Safety Outcome) | Number of days alive and without delirium or coma before 28 days to study day 28 | Enrollment to 28 days |
| Intensive Care Unit-free Days to Study Day 28 (Exploratory Clinical Outcome) | Number of days alive and free from intensive care unit admission after the final transfer out of the intensive care unit before 28 days to study day 28 | Enrollment to 28 days |
| Hospital-Free Days to Study Day 28 (Exploratory Clinical Outcome) | Number of days alive and free from hospitalization after the final transfer out of the hospital before 28 days to study day 28 | Enrollment to 28 days |
| In-hospital Mortality to Study Day 28 (Exploratory Clinical Outcome) | All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment | Enrollment to 28 days |
| Derived |
| 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. Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial. CHEST Crit Care. 2024 Mar;2(1):100033. doi: 10.1016/j.chstcc.2023.100033. Epub 2023 Nov 25. |
| 37546787 | Derived | 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. Protocol and statistical analysis plan for the Mode of Ventilation During Critical IllnEss (MODE) trial. medRxiv [Preprint]. 2023 Jul 24:2023.07.21.23292998. doi: 10.1101/2023.07.21.23292998. |
During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation.
| BG002 | Adaptive Pressure Control Mode | During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation. |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Pressure Control Mode |
During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation. |
| OG002 | Adaptive Pressure Control Mode | During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation. |
|
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| Other Pre-specified | Exposure to Assigned Study Mode in First 3 Days (Feasibility Outcome) | Percentage of time in the assigned mode while receiving invasive mechanical ventilation in the study ICU between enrollment and 72 hours after enrollment. | Data not available for 3 patients: 1 in Volume Control group and 2 in Adaptive Pressure Control group. | Posted | Median | Inter-Quartile Range | Percentage of time | Enrollment to 72 hours |
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| Other Pre-specified | Adherence to Study Mode in First 3 Days (Feasibility Outcome) | Percentage of time in the assigned mode while receiving invasive mechanical ventilation in the study ICU with a mandatory mode between enrollment and 72 hours after enrollment (excluding time spent in spontaneous modes). | Sixteen patients did not have a recorded mandatory mode of ventilation during the study period from enrollment to death or extubation: 5 in Volume Control group, 4 in Pressure Control group, and 7 in Adaptive Pressure Control group. | Posted | Median | Inter-Quartile Range | Percentage of time | Enrollment to 72 hours |
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| Other Pre-specified | Time From Enrollment to Initiation of Assigned Mode of Mechanical Ventilation (Feasibility Outcome) | Nineteen patients did not have receipt of the assigned study mode recorded from enrollment to death or extubation: 7 in Volume Control group, 5 in Pressure Control group, and 7 in Adaptive Pressure Control group. | Posted | Median | Inter-Quartile Range | Hours | Enrollment to 28 days |
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| Other Pre-specified | Number of Patients With a "Mode Modification Sheet" Completed by Treating Clinicians (Feasibility Outcome) | Posted | Count of Participants | Participants | Enrollment to 28 days |
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| Other Pre-specified | Exhaled Tidal Volume (mL/kg Predicted Body Weight) (Exploratory Efficacy and Safety Outcome) | No tidal volume data were available for one patient in the Adaptive Pressure Control group. | Posted | Median | Inter-Quartile Range | mL / kg of predicted body weight | Enrollment to the first of extubation, 28 days, or death |
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| Other Pre-specified | Percentage of Exhaled Tidal Volumes Above Target Range (Exploratory Efficacy and Safety Outcome) | Percentage of exhaled tidal volume values above target range (>8mL/kg predicted body weight), reported as a percentage. | Tidal volume data were not available for one patient in the Adaptive Pressure Control group. | Posted | Median | Inter-Quartile Range | Percentage of time | Enrollment to the first of extubation, 28 days, or death |
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| Other Pre-specified | Hypoxemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) | Hypoxemia during mechanical ventilation defined as an SpO2 <85% for more than 5 minutes | Posted | Count of Participants | Participants | Enrollment to the first of 28 days or death |
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| Other Pre-specified | Severe Acidemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) | Severe acidemia during mechanical ventilation: pH < 7.1 on blood gas | Posted | Count of Participants | Participants | Enrollment to 28 days |
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| Other Pre-specified | Number of Blood Gas Laboratory Tests on the First Study Day (Exploratory Safety and Efficacy Outcome) | Posted | Median | Inter-Quartile Range | count of blood gas laboratory tests | Enrollment to 1 day |
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| Other Pre-specified | Pneumomediastinum or Pneumothorax During Mechanical Ventilation (Exploratory Efficacy and Safety Outcome) | Posted | Count of Participants | Participants | Enrollment to 28 days |
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| Other Pre-specified | SOFA Score on the First Study Day (Exploratory Safety and Efficacy Outcome) | The Sequential Organ Failure Assessment (SOFA) score is composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction or failure. Scores range from 0 (no evidence of organ dysfunction or failure) to 24 (evidence of severe organ dysfunction or failure). The mean of SOFA scores on study day 1 was calculated for each patient. | Insufficient data were available for four patients: 2 patients in the Volume Control group and 2 patients in the Pressure Control group. | Posted | Median | Inter-Quartile Range | SOFA Score | Enrollment to 1 day |
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| Other Pre-specified | Delirium and Coma Free Days to Day 28 (Exploratory Efficacy and Safety Outcome) | Number of days alive and without delirium or coma before 28 days to study day 28 | Posted | Median | Inter-Quartile Range | Delirium and coma-free days to day 28 | Enrollment to 28 days |
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| Other Pre-specified | Intensive Care Unit-free Days to Study Day 28 (Exploratory Clinical Outcome) | Number of days alive and free from intensive care unit admission after the final transfer out of the intensive care unit before 28 days to study day 28 | Posted | Median | Inter-Quartile Range | ICU-free days to day 28 | Enrollment to 28 days |
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| Other Pre-specified | Hospital-Free Days to Study Day 28 (Exploratory Clinical Outcome) | Number of days alive and free from hospitalization after the final transfer out of the hospital before 28 days to study day 28 | Posted | Median | Inter-Quartile Range | Hospital-free days to day 28 | Enrollment to 28 days |
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| Other Pre-specified | In-hospital Mortality to Study Day 28 (Exploratory Clinical Outcome) | All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment | Posted | Count of Participants | Participants | Enrollment to 28 days |
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| 59 |
| 181 |
| 0 |
| 181 |
| 0 |
| 181 |
| EG001 | Pressure Control Mode | During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation. | 67 | 198 | 0 | 198 | 0 | 198 |
| EG002 | Adaptive Pressure Control Mode | During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation. | 60 | 187 | 0 | 187 | 0 | 187 |
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