Protocolized Post-Extubation Respiratory Support Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Protocolized Post-Extubation Respiratory Support (PROPER) Study

Conditions
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Mechanical Ventilation Complication, Acute Respiratory Failure, Intubation Complication

Intervention / Treatment
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* Other: Protocolized post-extubation respiratory support
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is located in a participating unit Patient undergoing extubation from mechanical ventilation Patient has been receiving mechanical ventilation for at least 12 hours Age ≥ 18 years old Exclusion Criteria: Patient is receiving ventilation via a tracheostomy Patient is being extubated to comfort measures or has Do Not Reintubate order in place at the time of extubation Patient has required reintubation after a prior attempt at extubation during this hospitalization Unplanned or self-extubation, where immediate reintubation is deemed necessary by the clinical team

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protocolized Post-extubation Respiratory Support<br>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 | Other: Protocolized post-extubation respiratory support<br>* 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<br>|
| Active Comparator: Usual Care<br>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. | Other: Usual Care<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | within 96 hours of extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause In-hospital Death | All cause mortality, censored at the first of hospital discharge or 28 days after extubation | from extubation to discharge or 28 days post-extubation | 
| ICU-free Days | number of days alive from final ICU transfer until study day 28 | from extubation to discharge or 28 days post-extubation | 
| Ventilator-free Days | number of days alive from final invasive mechanical ventilation until study day 28 | from extubation to discharge or 28 days post-extubation | 
| Time to Reintubation | Time from extubation to reintubation | from extubation to discharge or 28 days post-extubation | 
| Number of Patients Requiring Re-intubation for Respiratory Indication | Number of patients in each group with respiratory indication for reintubation. | within 96 hours of extubation | 
| Number of Patients Requiring Reintubation for Laryngeal Edema | Percentage of patients in each group with laryngeal edema as the indication for reintubation | within 96 hours of extubation | 
| 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. | within 96 hours of extubation | 
| Number of Patients With Agitation | As defined by RAS score and reported by bedside nurse | within 96 hours of extubation | 
| Lowest S/F Ratio | Lowest ratio of O2 saturation to concentration inhaled oxygen (FIO2) | between 0-6 hours, 6-12 hours, and 12-24 hours after extubation | 
| Highest Respiratory Rate | Highest respiratory rate | between 0-6 hours, 6-12 hours, and 12-24 hours after extubation | 
| 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 | from 24 hours post extubation to 96 hours post-extubation |