Protocolized Post-Extubation Respiratory Support Study (PROPER)

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.

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.

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

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.

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

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.

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

Proportion of patients in each group with respiratory vs non-respiratory indications for reintubation

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

Data dictionary will be available upon requests. Requests for deidentified patient-level data will be reviewed by the trial steering committee. Sharing of deidentified data will require approval of proposed secondary analysis and a signed data use agreement.

Casey JD, Vaughan EM, Lloyd BD, Billas PA, Jackson KE, Hall EJ, Toporek AH, Buell KG, Brown RM, Richardson RK, Rooks JC, Buie RB, Wang L, Lindsell CJ, Ely EW, Self WH, Bernard GR, Rice TW, Semler MW. Protocolized Postextubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial. Am J Respir Crit Care Med. 2021 Aug 1;204(3):294-302. doi: 10.1164/rccm.202009-3561OC.

Casey JD, Vaughan ER, Lloyd BD, Bilas PA, Hall EJ, Toporek AH, Buell KG, Brown RM, Richardson RK, Rooks JC, Wang L, Lindsell CJ, Ely EW, Self WH, Bernard GR, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Protocolized Post-Extubation Respiratory Support to prevent reintubation: protocol and statistical analysis plan for a clinical trial. BMJ Open. 2019 Aug 2;9(8):e030476. doi: 10.1136/bmjopen-2019-030476.