NCT05563779: MODE

Mode Of Ventilation During Critical IllnEss Pilot Trial

Completed NA Results posted Last updated 23 February 2026

What this trial tests

NA trial testing Volume Control mode in Respiratory Failure in 566 participants. Completed in 28 August 2023.

Timeline

1 November 2022

Primary endpoint
28 August 2023

28 August 2023

Quick facts

Lead sponsor	Vanderbilt University Medical Center
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	treatment
Enrollment	566
Start date	1 November 2022
Primary completion	28 August 2023
Estimated completion	28 August 2023
Sites	1 location across United States

Drugs / interventions tested

• Volume Control mode
• Pressure Control mode
• Adaptive Pressure Control mode

Conditions studied

• Respiratory Failure — all drugs for Respiratory Failure →

Sponsor

Vanderbilt University Medical Center

Who can join

18 and older, any sex, with Respiratory Failure. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Ventilator-free Days (VFDs) to Day 28 After Enrollment Primary · Enrollment to 28 days

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.

Group	Value	95% CI
Volume Control Mode	23	0 – 26
Pressure Control Mode	22	0 – 26
Adaptive Pressure Control Mode	24	0 – 26

Exposure to Assigned Study Mode in First 3 Days (Feasibility Outcome) Secondary · Enrollment to 72 hours

Percentage of time in the assigned mode while receiving invasive mechanical ventilation in the study ICU between enrollment and 72 hours after enrollment.

Group	Value	95% CI
Volume Control Mode	87.5	61.0 – 98.4
Pressure Control Mode	90.2	56.6 – 98.9
Adaptive Pressure Control Mode	93.8	74.2 – 99.7

Adherence to Study Mode in First 3 Days (Feasibility Outcome) Secondary · Enrollment to 72 hours

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).

Group	Value	95% CI
Volume Control Mode	100.0	100.0 – 100.0
Pressure Control Mode	100.0	98.9 – 100.0
Adaptive Pressure Control Mode	100.0	100.0 – 100.0

Time From Enrollment to Initiation of Assigned Mode of Mechanical Ventilation (Feasibility Outcome) Secondary · Enrollment to 28 days

Group	Value	95% CI
Volume Control Mode	5.2	1.7 – 16.6
Pressure Control Mode	5.2	1.4 – 17.1
Adaptive Pressure Control Mode	4.6	0.8 – 15.1

Number of Patients With a "Mode Modification Sheet" Completed by Treating Clinicians (Feasibility Outcome) Secondary · Enrollment to 28 days

Group	Value	95% CI
Volume Control Mode	19
Pressure Control Mode	25
Adaptive Pressure Control Mode	4

Exhaled Tidal Volume (mL/kg Predicted Body Weight) (Exploratory Efficacy and Safety Outcome) Secondary · Enrollment to the first of extubation, 28 days, or death

Group	Value	95% CI
Volume Control Mode	6.2	5.9 – 7.1
Pressure Control Mode	6.4	5.8 – 7.4
Adaptive Pressure Control Mode	6.2	5.9 – 6.9

Percentage of Exhaled Tidal Volumes Above Target Range (Exploratory Efficacy and Safety Outcome) Secondary · Enrollment to the first of extubation, 28 days, or death

Percentage of exhaled tidal volume values above target range (\>8mL/kg predicted body weight), reported as a percentage.

Group	Value	95% CI
Volume Control Mode	0.0	0.0 – 8.3
Pressure Control Mode	6.8	0.0 – 31.4
Adaptive Pressure Control Mode	3.6	0.0 – 14.3

Hypoxemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) Secondary · Enrollment to the first of 28 days or death

Hypoxemia during mechanical ventilation defined as an SpO2 \<85% for more than 5 minutes

Group	Value	95% CI
Volume Control Mode	21
Pressure Control Mode	20
Adaptive Pressure Control Mode	14

Severe Acidemia During Mechanical Ventilation (Exploratory Safety and Efficacy Outcome) Secondary · Enrollment to 28 days

Severe acidemia during mechanical ventilation: pH \< 7.1 on blood gas

Group	Value	95% CI
Volume Control Mode	22
Pressure Control Mode	21
Adaptive Pressure Control Mode	14

Number of Blood Gas Laboratory Tests on the First Study Day (Exploratory Safety and Efficacy Outcome) Secondary · Enrollment to 1 day

Group	Value	95% CI
Volume Control Mode	3	1 – 5
Pressure Control Mode	2	1 – 5
Adaptive Pressure Control Mode	3	1 – 5

Pneumomediastinum or Pneumothorax During Mechanical Ventilation (Exploratory Efficacy and Safety Outcome) Secondary · Enrollment to 28 days

Group	Value	95% CI
Volume Control Mode	4
Pressure Control Mode	6
Adaptive Pressure Control Mode	1

SOFA Score on the First Study Day (Exploratory Safety and Efficacy Outcome) Secondary · Enrollment to 1 day

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.

Group	Value	95% CI
Volume Control Mode	11.0	8.4 – 13.9
Pressure Control Mode	11.9	8.5 – 14.0
Adaptive Pressure Control Mode	11.0	8.4 – 13.9

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial.
   Seitz KP, Lloyd BD, Wang L, Shotwell MS, et al · · 2025 · cited 3× · PMID 40189043 · DOI 10.1016/j.chest.2025.03.024
2. Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial.
   Seitz KP, Lloyd BD, Wang L, Shotwell MS, et al · · 2024 · cited 3× · PMID 38742219 · DOI 10.1016/j.chstcc.2023.100033
3. Protocol and statistical analysis plan for the Mode of Ventilation During Critical IllnEss (MODE) trial
   Seitz KP, Lloyd BD, Wang L, Shotwell MS, et al · · 2023 · DOI 10.1101/2023.07.21.23292998