Acute Respiratory Failure, Critically Ill
Conditions
Keywords
Proportional Assist Ventilation, Pressure Support Ventilation, Weaning
Brief summary
For adult patients with acute respiratory failure requiring invasive mechanical ventilation, does a ventilation strategy using proportional assist ventilation with load-adjustable gain factors (PAV+) result in a shorter duration of time spent on mechanical ventilation than a ventilation strategy using pressure support ventilation (PSV)?
Detailed description
Patients with acute respiratory failure require mechanical ventilation to help them breathe until they recover from their acute illness. Although mechanical ventilation is necessary to sustain life in such situations, it can induce weakness of the respiratory muscles which may lead to prolonged dependence on the ventilator. Prolonged dependence on mechanical ventilation is associated with increased mortality, morbidity and costs to the healthcare system. Thus, a main goal of assisted mechanical ventilation is to reduce the patient's respiratory distress while maintaining some respiratory muscle activity. To attain this goal, the amount of ventilator assistance should theoretically be adjusted to target normal or reasonable levels of respiratory effort. Modes of Mechanical Ventilation: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mode of mechanical ventilation which delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a reasonable range. This is the only mode of ventilation which allows for measurement and targeting of a specific range of respiratory muscle activity by the patient. Pressure support ventilation (PSV) is a mode of ventilation which is considered the current standard of care for assisting breathing of patients during the recovery phase of acute respiratory failure. Several studies have shown short term advantages of PAV over PSV, including improved patient-ventilator synchronization, improved adaptability to changes in patient effort, and improved sleep quality. Goal of this Randomized Controlled Trial: To demonstrate that for patients with acute respiratory failure, ventilation with PAV+, being more physiological, will result in a shorter duration of time spent on mechanical ventilation than ventilation with PSV.
Interventions
OTHERPSV ventilation strategy
An algorithm for adjusting the level of pressure support according to usual clinical parameters; patients not tolerating PSV will be switched to Assist/Control mode according to predefined criteria
OTHERPAV+ ventilation strategy
An algorithm for adjusting the level of support (gain) to maintain a predefined range of respiratory muscle pressure; patients not tolerating PAV+ (Puritan Bennett™ 840 or 980 ventilator) will be switched to Assist/Control mode according to predefined criteria
Sponsors
Canadian Institutes of Health Research (CIHR)
Medtronic
Canadian Critical Care Trials Group
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A staged enrolment process will be used to identify patients eligible to be enrolled and randomized in the study. At each stage of the enrolment process, a patient must meet inclusion criteria and not meet
Exclusion criteria
in order to pass. To progress to the next stage, patients must continue to pass criteria from the prior stages. After enrolment, there are also specific tests to perform (with pass/fail criteria) to determine eligibility to be randomized. A. SCREENING INCLUSION CRITERIA: * A1. Age 18 years or older * A2. Intubated and receiving any mode of invasive mechanical ventilation ≥ 24 hours A. SCREENING
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to successful liberation from invasive mechanical ventilation. | up to 90 days | Successful liberation is defined as removal of the endotracheal tube AND remaining alive with no need for reintubation/reinstitution of invasive mechanical ventilation for 7 days post extubation, or until successful ICU discharge, or until live hospital discharge, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to live ICU discharge (up to day 90) | up to 90 days | Patients will remain in the study and will continue on the assigned ventilation strategy until: successful extubation, successful ICU discharge, live hospital discharge, death, or 90 days post randomization, whichever comes first. |
| Time from randomization to live hospital discharge (up to day 90) | up to 90 days | Patients will remain in the study and will continue on the assigned ventilation strategy until: successful extubation, successful ICU discharge, live hospital discharge, death, or 90 days post randomization, whichever comes first. |
| Mortality | up to 90 days | Measured as time to death, ICU mortality; hospital mortality; 21, 28, and 90 day mortality |
| Weaning Progress | up to 90 days | Measured as time from randomization to: first SBT; first successful SBT; first extubation |
| Weaning Difficulties | 90 days | Measured as the number of patients failing first SBT or first extubation attempt and requiring up to 7 days to extubate (difficult weaning group/group 2); failing first SBT or first extubation attempt and requiring more than 7 days to extubate (prolonged weaning group/group 3) |
| Weaning Complications | 90 days | Measured as the number of patients: requiring non-invasive ventilation post-extubation; ventilated more than 7 days post randomization, ventilated more than 21 days from time of intubation (prolonged MV group); receiving tracheostomy post-randomization, requiring re-intubation (up to 7d after planned extubation) |
| Tolerance of modes | 90 days | Measured as number of patients ever requiring A/C mode post randomization; number of patient-days requiring A/C mode post randomization |
| Serious Adverse Events | 90 days | Incidence of reported serious adverse events |
| Ventilator-free days at 14, 21 and 28 days post randomization | 14, 21 and 28 days post randomization | Ventilator-free days (VFDs) are defined as the number of days alive and free of INVASIVE ventilation post SUCCESSFUL EXTUBATION or post successful termination of invasive mechanical ventilation (MV) from time of randomization to day 21 post randomization. Successful extubation is defined as removal of the endotracheal tube AND remaining alive with no need for reintubation/reinstitution of invasive mechanical ventilation for 7 days post extubation, or until successful ICU discharge, or until live hospital discharge, whichever comes first. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subgroup analyses based on (b) failing an SBT prior to randomization vs. failed CPAP 0 trial vs. failed weaning criteria prior to randomization | At randomization | Identifies a subgroup of patients at time of randomization classified as difficult weaning vs. failed CPAP 0 trial vs. failed weaning criteria prior to randomization |
| Subgroup analyses based on (c) failed extubation prior to randomization | At randomization | Identifies a subgroup of patients at time of randomization classified as having difficult weaning. |
| Subgroup analyses based on (d) mild vs. moderate vs. severe frailty | At ICU admission | Differentiates between severely frail and less frail |
| Subgroup analyses based on COVID-19 positive test | At ICU admission | Differentiates between COVID-19 positive and COVID-19 negative |
| Subgroup analyses based on tracheostomy present at randomization | At randomization | Identifies a subgroup of patients at risk of prolonged weaning |
| Subgroup analyses based on: (a) duration of MV prior to randomization as a continuous variable or as a binary variable of greater than 5 days | At randomization | Identifies a subgroup of patients at time of randomization who are at risk for prolonged weaning |
| Co-interventions | 28 days | Co-interventions will be monitored and described including use of sedating medications |
Countries
Argentina, Canada, France, Greece, Italy, Saudi Arabia, Spain
Outcome results
None listed