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CompletedNCT03288311PROPERUpdated Dec 29, 2023Results posted

Protocolized Post-Extubation Respiratory Support Study

An interventional study of Protocolized post-extubation respiratory support and Usual Care in Mechanical Ventilation Complication, Acute Respiratory Failure and Intubation Complication, sponsored by Vanderbilt University Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-29.

Sponsored by Vanderbilt University Medical Center · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
751
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Mechanical Ventilation Complication
  • Acute Respiratory Failure
  • Intubation Complication
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Outcomes assessor)
Enrollment
751 participants (actual)

Study arms

  • 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

  • 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

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.

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. Time to Reintubation

    Time from extubation to reintubation

    Time frame: from extubation to discharge or 28 days post-extubation

  5. 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

  6. 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

  7. 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

  8. Number of Patients With Agitation

    As defined by RAS score and reported by bedside nurse

    Time frame: within 96 hours of extubation

  9. 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

  10. Highest Respiratory Rate

    Highest respiratory rate

    Time frame: between 0-6 hours, 6-12 hours, and 12-24 hours after extubation

  11. 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

06

Results

Posted Dec 29, 2023

Participant flow

Participant flow — Overall Study
MilestoneProtocolized Post-extubation Respiratory SupportUsual Care
Started359392
Completed359392
Not completed00

Outcome measures

PrimaryReintubation

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
Reported as:
Count of participants · Participants
Reintubation
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
Reintubation5752
SecondaryAll-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
Reported as:
Count of participants · Participants
All-cause In-hospital Death
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
All-cause In-hospital Death2941
SecondaryICU-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
Reported as:
Median · days
ICU-free Days
daysProtocolized Post-extubation Respiratory SupportUsual Care
ICU-free Days26 (23 to 26)26 (22 to 26)
SecondaryVentilator-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
Reported as:
Median · days
Ventilator-free Days
daysProtocolized Post-extubation Respiratory SupportUsual Care
Ventilator-free Days28 (28 to 28)28 (28 to 28)
SecondaryTime to Reintubation

Time from extubation to reintubation

Time frame:
from extubation to discharge or 28 days post-extubation
Reported as:
Median · hours
Time to Reintubation
hoursProtocolized Post-extubation Respiratory SupportUsual Care
Time to Reintubation56 (21 to 147)47 (18 to 163)
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients Requiring Re-intubation for Respiratory Indication
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
Number of Patients Requiring Re-intubation for Respiratory Indication3533
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients Requiring Reintubation for Laryngeal Edema
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
Number of Patients Requiring Reintubation for Laryngeal Edema02
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Delirium
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
Number of Patients With Delirium160151
SecondaryNumber of Patients With Agitation

As defined by RAS score and reported by bedside nurse

Time frame:
within 96 hours of extubation

No measurements were reported for this outcome.

SecondaryLowest 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
Reported as:
Median · ratio of O2 saturation to concentration
Lowest S/F Ratio
ratio of O2 saturation to concentrationProtocolized Post-extubation Respiratory SupportUsual Care
0-6 hours237.5 (205.0 to 254.3)268.5 (224.4 to 344.4)
6-12 hours242.5 (222.5 to 303.3)318.5 (240.0 to 438.1)
12-24 hours242.5 (214.6 to 340.7)327.6 (240.0 to 438.1)
SecondaryHighest Respiratory Rate

Highest respiratory rate

Time frame:
between 0-6 hours, 6-12 hours, and 12-24 hours after extubation
Reported as:
Median · breaths per minute
Highest Respiratory Rate
breaths per minuteProtocolized Post-extubation Respiratory SupportUsual Care
0-6 hours23 (20 to 28)24 (21 to 28)
6-12 hours24 (19 to 28)24 (20 to 29)
12-24 hours25 (21 to 30)25 (21 to 29)
SecondaryUse 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
Reported as:
Count of participants · Participants
Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation
ParticipantsProtocolized Post-extubation Respiratory SupportUsual Care
Use of High Flow Nasal Cannula (HFNC) or Non-invasive Ventilation (NIV) Beyond 24 Hours Post-extubation2614

Adverse events

Collected over Adverse events were collected from enrollment to 28 days after enrollment. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Protocolized Post-extubation Respiratory Support29/359 (8.1%)0/359 (0%)0/359 (0%)
Usual Care41/392 (10.5%)0/392 (0%)0/392 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Protocolized Post-extubation Respiratory SupportUsual CareTotal
Median56 (43 to 66)57 (42 to 66)57 (42 to 66)
Sex: Female, Male
Sex: Female, Male(Participants)Protocolized Post-extubation Respiratory SupportUsual CareTotal
Female155187342
Male204205409
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Protocolized Post-extubation Respiratory SupportUsual CareTotal
White287317604
Black or African American5859117
Asian3811
Other549
Not Reported6410
07

Study locations

1 site
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37212, United States
08

References and documents

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. PubMed 33794131 ↗
  • 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. PubMed 31377713 ↗

Study documents

  • Protocol and statistical analysis plan · Jan 4, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

Supporting information: Study protocol, Sap

09

Registry details

Key details

Study ID
NCT03288311
Lead sponsor
Vanderbilt University Medical Center
Responsible party
Jonathan Casey (Pulmonary and Critical Care Medicine Research Fellow, Vanderbilt University Medical Center) — Principal investigator
First posted
Sep 20, 2017
Start date
Oct 1, 2017
Primary completion
Mar 31, 2019
Completion
Apr 28, 2019
Results posted
Dec 29, 2023
Last update
Dec 29, 2023

Study contacts

Todd W Rice, MD, MSc
study chair · Vanderbilt University Medical Center

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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