Protocolized Post-Extubation Respiratory Support Study (PROPER)

Protocolized Post-Extubation Respiratory Support (PROPER) Study

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.

Study Overview

• Status: Completed
• Conditions: Intubation Complication; Mechanical Ventilation Complication; Acute Respiratory Failure
• Intervention / Treatment: Other: Protocolized post-extubation respiratory support; Other: Usual Care

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.

• Study Type: Interventional
• Enrollment (Actual): 751
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Other: 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
Active Comparator: 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.	Other: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Study Chair: Todd W Rice, MD, MSc, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): April 28, 2019

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (Actual): September 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: 170650

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Data will be available following publication of the primary trial results
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No