Mode Of Ventilation During Critical IllnEss Pilot Trial (MODE)

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.

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).

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.

During invasive mechanical ventilation in a study location, Volume Control will be used as the mode for continuous mandatory ventilation.

During invasive mechanical ventilation in a study location, Pressure Control will be used as the mode for continuous mandatory ventilation.

During invasive mechanical ventilation in a study location, Adaptive Pressure Control will be used as the mode for continuous mandatory ventilation.

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.

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

Proportion 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)

Number of patients with a "Mode Modification Sheet" completed by treating clinicians (Feasibility Outcome)

Median daily exhaled tidal volume (mL/kg predicted body weight) on each study day (Exploratory Efficacy and Safety Outcome)

Proportion of recorded breaths with exhaled tidal volume values above target range (>8mL/kg predicted body weight) on each study day

Number of blood gas laboratory tests per day while receiving mechanical ventilation (Exploratory Safety and Efficacy Outcome)

Pneumomediastinum or pneumothorax during course of mechanical ventilation (Exploratory Efficacy and Safety 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

Number of days alive and free from hospitalization after the final transfer out of the hospital before 28 days to study day 28

Inclusion Criteria: Age ≥ 18 years Receiving mechanical ventilation through an endotracheal tube or tracheostomy Admitted to the study ICU Exclusion Criteria: Patient is pregnant Patient is a prisoner Patient receiving invasive mechanical ventilation at place of residence prior to hospital admission Patient receiving extracorporeal membrane oxygenation at the time of admission to the study ICU

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.