Acute Respiratory Failure, Intubation Complication, Mechanical Ventilation Complication
Conditions
Brief summary
Invasive mechanical ventilation is common in the medical intensive care unit, and the period of time following extubation remains high risk as 11 to 15% of patients require reintubation after their first extubation. Reintubation is associated with increased rates of nosocomial infection and is an independent predictor of mortality. Non-invasive ventilation and high flow nasal cannula are the only therapies that have been shown to reduce the rate of reintubation. Recent clinical trials suggest that all patients might benefit from some form of post-extubation respiratory support, but use of these therapies in usual care remains low. PROPER is a cluster-randomized, multiple-crossover trial comparing a respiratory therapist driven protocol to provide post-extubation respiratory support to all patients, compared to usual care. The trial will enroll patients undergoing extubation in the Medical ICU at Vanderbilt from October 2017 until March 2019. The primary outcome will be reintubation within 96 hours.
Detailed description
PROPER is a prospective, pragmatic, cluster-randomized, multiple-crossover trial comparing a respiratory therapist driven protocol for post-extubation respiratory support to usual care. The primary outcome will be reintubation by 96 hours. All adults (age 18 or older) who receive at least 12 hours of mechanical ventilation and are extubated in the Vanderbilt Medical ICU will be enrolled in the trial. The ICU will be divided into 2 clusters, based on the geographic areas covered by the two respiratory therapist dedicated to that ICU. The study will occur in three month blocks. One cluster will be randomized to receive protocolized post-extubation respiratory support (as prescribed by a protocol and delivered by a respiratory therapist), while the other cluster receives usual care, which can include post-extubation respiratory support when requested by the clinical team. At the end of three months, the clusters will cross-over, such that each cluster will spend half of the study receiving protocolized post-extubation respiratory and half of the study receiving usual care. It is anticipated that approximately 630 patients will be enrolled from the medical ICU during the 18 month study period.
Interventions
OTHERProtocolized post-extubation respiratory support
Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning
OTHERUsual Care
Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is located in a participating unit 2. Patient undergoing extubation from mechanical ventilation 3. Patient has been receiving mechanical ventilation for at least 12 hours 4. Age ≥ 18 years old
Exclusion criteria
1. Patient is receiving ventilation via a tracheostomy 2. Patient is being extubated to comfort measures or has Do Not Reintubate order in place at the time of extubation 3. Patient has required reintubation after a prior attempt at extubation during this hospitalization 4. Unplanned or self-extubation, where immediate reintubation is deemed necessary by the clinical team
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reintubation | within 96 hours of extubation | Any placement of an endotracheal tube for any indication within 96 hours of extubation, censored at the first of hospital discharge or 96 hours after extubation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Highest Respiratory Rate | between 0-6 hours, 6-12 hours, and 12-24 hours after extubation | Highest respiratory rate |
| All-cause In-hospital Death | from extubation to discharge or 28 days post-extubation | All cause mortality, censored at the first of hospital discharge or 28 days after extubation |
| ICU-free Days | from extubation to discharge or 28 days post-extubation | number of days alive from final ICU transfer until study day 28 |
| Ventilator-free Days | from extubation to discharge or 28 days post-extubation | number of days alive from final invasive mechanical ventilation until study day 28 |
| Time to Reintubation | from extubation to discharge or 28 days post-extubation | Time from extubation to reintubation |
| Lowest S/F Ratio | between 0-6 hours, 6-12 hours, and 12-24 hours after extubation | Lowest ratio of O2 saturation to concentration inhaled oxygen (FIO2) |
| Number of Patients Requiring Reintubation for Laryngeal Edema | within 96 hours of extubation | Percentage of patients in each group with laryngeal edema as the indication for reintubation |
| Number of Patients With Delirium | within 96 hours of extubation | As defined by Confusion Assessment Method for the ICU (CAM-ICU) score and reported by bedside nurse. A report of Yes indicates the presence of delirium, which is reflected in the reported cases. |
| Number of Patients With Agitation | within 96 hours of extubation | As defined by RAS score and reported by bedside nurse |
| Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation | from 24 hours post extubation to 96 hours post-extubation | Use of non-invasive ventilation or high flow nasal cannula beyond 24 hours post-extubation |
| Number of Patients Requiring Re-intubation for Respiratory Indication | within 96 hours of extubation | Number of patients in each group with respiratory indication for reintubation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Protocolized Post-extubation Respiratory Support Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning
Protocolized post-extubation respiratory support: Qualifying patients undergoing extubation in an ICU bed randomized to post-extubation respiratory support will receive either non-invasive ventilation or high flow nasal cannula (as determined by a prespecified protocol and applied by a respiratory therapist) from the time of extubation until 5AM the following morning | 359 |
| Usual Care Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team.
Usual Care: Qualifying patients undergoing extubation in an ICU bed randomized to usual care will receive standard-of-care treatment, which may include post-extubation respiratory support at the discretion of their clinical team. | 392 |
| Total | 751 |
Baseline characteristics
| Characteristic | Protocolized Post-extubation Respiratory Support | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 57 years | 57 years |
| Race/Ethnicity, Customized Asian | 3 Participants | 8 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 58 Participants | 59 Participants | 117 Participants |
| Race/Ethnicity, Customized Not Reported | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 287 Participants | 317 Participants | 604 Participants |
| Sex: Female, Male Female | 155 Participants | 187 Participants | 342 Participants |
| Sex: Female, Male Male | 204 Participants | 205 Participants | 409 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 359 | 41 / 392 |
| other Total, other adverse events | 0 / 359 | 0 / 392 |
| serious Total, serious adverse events | 0 / 359 | 0 / 392 |
Outcome results
Primary
Reintubation
Any placement of an endotracheal tube for any indication within 96 hours of extubation, censored at the first of hospital discharge or 96 hours after extubation
Time frame: within 96 hours of extubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Reintubation | 57 Participants |
| Usual Care | Reintubation | 52 Participants |
Secondary
All-cause In-hospital Death
All cause mortality, censored at the first of hospital discharge or 28 days after extubation
Time frame: from extubation to discharge or 28 days post-extubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | All-cause In-hospital Death | 29 Participants |
| Usual Care | All-cause In-hospital Death | 41 Participants |
Secondary
Highest Respiratory Rate
Highest respiratory rate
Time frame: between 0-6 hours, 6-12 hours, and 12-24 hours after extubation
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Protocolized Post-extubation Respiratory Support | Highest Respiratory Rate | 0-6 hours | 23 breaths per minute |
| Protocolized Post-extubation Respiratory Support | Highest Respiratory Rate | 6-12 hours | 24 breaths per minute |
| Protocolized Post-extubation Respiratory Support | Highest Respiratory Rate | 12-24 hours | 25 breaths per minute |
| Usual Care | Highest Respiratory Rate | 0-6 hours | 24 breaths per minute |
| Usual Care | Highest Respiratory Rate | 6-12 hours | 24 breaths per minute |
| Usual Care | Highest Respiratory Rate | 12-24 hours | 25 breaths per minute |
Secondary
ICU-free Days
number of days alive from final ICU transfer until study day 28
Time frame: from extubation to discharge or 28 days post-extubation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | ICU-free Days | 26 days |
| Usual Care | ICU-free Days | 26 days |
Secondary
Lowest S/F Ratio
Lowest ratio of O2 saturation to concentration inhaled oxygen (FIO2)
Time frame: between 0-6 hours, 6-12 hours, and 12-24 hours after extubation
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Protocolized Post-extubation Respiratory Support | Lowest S/F Ratio | 0-6 hours | 237.5 ratio of O2 saturation to concentration |
| Protocolized Post-extubation Respiratory Support | Lowest S/F Ratio | 6-12 hours | 242.5 ratio of O2 saturation to concentration |
| Protocolized Post-extubation Respiratory Support | Lowest S/F Ratio | 12-24 hours | 242.5 ratio of O2 saturation to concentration |
| Usual Care | Lowest S/F Ratio | 12-24 hours | 327.6 ratio of O2 saturation to concentration |
| Usual Care | Lowest S/F Ratio | 0-6 hours | 268.5 ratio of O2 saturation to concentration |
| Usual Care | Lowest S/F Ratio | 6-12 hours | 318.5 ratio of O2 saturation to concentration |
Secondary
Number of Patients Requiring Reintubation for Laryngeal Edema
Percentage of patients in each group with laryngeal edema as the indication for reintubation
Time frame: within 96 hours of extubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Number of Patients Requiring Reintubation for Laryngeal Edema | 0 Participants |
| Usual Care | Number of Patients Requiring Reintubation for Laryngeal Edema | 2 Participants |
Secondary
Number of Patients Requiring Re-intubation for Respiratory Indication
Number of patients in each group with respiratory indication for reintubation.
Time frame: within 96 hours of extubation
Population: Full trial population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Number of Patients Requiring Re-intubation for Respiratory Indication | 35 Participants |
| Usual Care | Number of Patients Requiring Re-intubation for Respiratory Indication | 33 Participants |
Secondary
Number of Patients With Agitation
As defined by RAS score and reported by bedside nurse
Time frame: within 96 hours of extubation
Population: Data was unavailable for collection
Secondary
Number of Patients With Delirium
As defined by Confusion Assessment Method for the ICU (CAM-ICU) score and reported by bedside nurse. A report of Yes indicates the presence of delirium, which is reflected in the reported cases.
Time frame: within 96 hours of extubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Number of Patients With Delirium | 160 Participants |
| Usual Care | Number of Patients With Delirium | 151 Participants |
Secondary
Time to Reintubation
Time from extubation to reintubation
Time frame: from extubation to discharge or 28 days post-extubation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Time to Reintubation | 56 hours |
| Usual Care | Time to Reintubation | 47 hours |
Secondary
Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation
Use of non-invasive ventilation or high flow nasal cannula beyond 24 hours post-extubation
Time frame: from 24 hours post extubation to 96 hours post-extubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation | 26 Participants |
| Usual Care | Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation | 14 Participants |
Secondary
Ventilator-free Days
number of days alive from final invasive mechanical ventilation until study day 28
Time frame: from extubation to discharge or 28 days post-extubation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocolized Post-extubation Respiratory Support | Ventilator-free Days | 28 days |
| Usual Care | Ventilator-free Days | 28 days |