Clinical trial NCT05506904: Liberation From Mechanical Ventilation Using Extubation Advisor Decision Support
Official title: Liberation From Mechanical Ventilation Using Extubation Advisor Decision Support: The Multicentre (LEADS) Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Airway Extubation
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2022-08-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre pragmatic vanguard pilot RCT of the EA tool in invasive ventilated critically ill patients, with and without COVID-19. Individual patients will be randomized (1:1) to intervention (EA tool) or control (standard care).
Primary purpose: PREVENTION

Brief summary: Timely and safe extubation in critically ill patients is vitally important as prolonged mechanical ventilation and failed attempts at extubation are associated with increased morbidity, mortality, costs, intensive care unit (ICU) stays, and a risk for aerosolization of COVID-19 to health care providers. A Spontaneous Breathing Trial (SBT) is the current standard of care to assess a patient's readiness for extubation. However, SBTs are performed in various ways and have poor ability to predict successful extubation on their own. There is an urgent need to improve and standardize extubation decision-making. In a prior multicenter study, the investigators showed that decreased respiratory rate variability during SBTs predicted extubation failure better than other predictive indices.

The Extubation Advisor (EA) tool combines clinician's assessments of extubation readiness with predictive analytics and risk mitigation strategies for individual patients. In a single centre observational study, the investigators demonstrated the ability to deliver EA reports to the bedside and acceptability of this decision-support tool to respiratory therapists (RTs) and physicians (MDs).

The investigators will conduct the Liberation from mechanical ventilation using EA Decision Support (LEADS) Pilot Trial to assess feasibility outcomes. They will include critically ill adults who are invasively ventilated for \>48 hours and are ready to undergo an SBT.

Patients in the intervention arm undergo an EA assessment and treating clinicians (RTs, MDs) will receive an EA report for each SBT conducted. The EA report will help to guide extubation decision-making. Patients in the control arm receive standard care. SBTs will be directed by clinicians.

The primary feasibility outcome will reflect the ability to recruit the desired population. The investigators will also assess the usefulness of the tool to MDs and complete an analysis of resource utilization to inform future economic analyses of cost-effectiveness. The investigators aim to recruit 1 to 2 patients/month/center.

The LEADS trial is novel and low-risk. It is the first trial to evaluate use of a bedside decision support tool to assist ICU clinicians with extubation decision-making. The LEADS pilot trial will inform the design of a future, large-scale randomized controlled trial that is expected to enhance the care delivered to critically ill patients, improve extubation outcomes, and inform extubation practice in ICUs.

Detailed description: Background: Timely and safe extubation (i.e. endotracheal tube removal) in critically ill patients is vitally important as prolonged mechanical ventilation and failed attempts at extubation (i.e. re-intubation\<48 hrs; 15% incidence) are associated with increased morbidity, mortality, costs, intensive care unit (ICU) stays, and a risk for aerosolization of COVID-19 to health care providers. A Spontaneous Breathing Trial (SBT) is the current standard of care to assess a patient's readiness for extubation. However, SBTs are performed in various ways and have poor ability to predict successful extubation on their own. There is an urgent need to improve and standardize extubation decision-making in the intensive care unit. In a prior multicenter study (n=721), the investigators showed that decreased respiratory rate variability during SBTs predicted extubation failure better than other predictive indices. The Extubation Advisor (EA) tool combines clinician's assessments of extubation readiness with predictive analytics and risk mitigation strategies for individual patients. In a single centre observational study (n=117; 2 ICUs), the investigators demonstrated the ability to deliver EA reports to the bedside and acceptability of this decision-support tool to respiratory therapists (RTs) and physicians (MDs).

Proposed Trial: The investigators will conduct the Liberation from mechanical ventilation using EA Decision Support (LEADS) Pilot Trial to assess feasibility outcomes including recruitment of critically ill patients with and without COVID-19 and protocol adherence.

Patients: The investigators will include critically ill adults who are invasively ventilated for \>48 hours and who are ready to undergo an SBT with a view to extubation.

Intervention: Patients in the intervention arm will undergo an EA assessment and treating clinicians (RTs, MDs) will receive an EA report for each SBT conducted. The EA report will help to guide, rather than direct extubation decision-making by MDs.

Control: Patients in the control arm will receive standard care. SBTs will be directed by clinicians, using current best evidence. No EA assessments will be made, and no EA reports will be generated.

Outcomes: The primary feasibility outcome will reflect the ability to recruit the desired population. Secondary feasibility outcomes will assess rates of (i) consent (for eligible patients approached), (ii) randomization, (iii) intervention adherence, (iv) crossovers (EA to standard care and standard care to EA), and (v) completeness of clinical outcomes collected. The investigators will also assess the usefulness of the tool to MDs and complete an analysis of resource utilization to inform future economic analyses of cost-effectiveness. The investigators aim to recruit 1 to 2 patients/month/center on average. The investigators aim to achieve \>75% consent rate, \>95% randomization rate in consented patients, \>80% of EA reports generated and delivered (intervention arm), \<10% crossovers (both arms), and \>90% of patients with complete clinical outcomes. The investigators will report feasibility outcomes overall and by site.

Impact: The LEADS trial was informed by extensive preparatory work conducted within two parallel programs of research on weaning and extubation. The LEADS trial is novel and low-risk. It is the first trial to evaluate use of a bedside decision support tool to assist ICU clinicians with extubation decision-making. The LEADS pilot trial will inform the design of a future, large-scale randomized controlled trial that is expected to enhance the care delivered to critically ill patients, improve extubation outcomes, and inform extubation practice in ICUs.

Eligibility criteria: Inclusion Criteria:

* With or without COVID-19
* In the intensive care unit (ICU)
* Able to provide informed consent (through a surrogate)
* Critically ill adults (age≥18)
* Anticipated to need invasive ventilation for \>48 hours prior to an initial SBT
* Ready to undergo an initial SBT within the next 24 hours with a view to extubation as per treating MDs. As per the FAST trial, an SBT will be defined as a focused assessment on low ventilator settings \[T-piece, continuous positive airway pressure (CPAP), or PS \< 8 cm H2O regardless of positive end-expiratory pressure (PEEP)\]

Exclusion Criteria:

* Suffer from known or suspected peripheral severe myopathy or neuropathy, or limb weakness or paralysis or central (e.g., post arrest, large intracranial stroke or bleed) injury or Glasgow Coma Scale (GCS) \< 6
* Do not wish to be re-intubated as part of their treatment goals
* Were previously extubated during the same ICU admission
* Have undergone 1 or more SBTs
* Already have a tracheostomy
* Are moribund or expected to die.

Primary outcomes:
measure: Evaluate the feasibility of enrolling 1-2 patients per centre per month
timeFrame: Upon study completion, 12 months after study initiation
Secondary outcomes:
measure: Evaluate feasibility of consenting greater than 75% of eligible patients
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate feasibility of randomizing greater the 95% of consented patients
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate feasibility of generating and delivering greater than 80% of EA reports to the attending physician
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate feasibility of crossovers between the intervention and control arms occurring less than 10% of the time
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate feasibility of collecting complete patient outcomes greater than 90% of the time
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate usefulness of EA reports
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate institutional costs required to implement the EA device
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate the time required by respiratory therapists to implement the EA device
timeFrame: Upon study completion, 12 months after study initiation
measure: Evaluate the time required by research coordinators to implement the EA device
timeFrame: Upon study completion, 12 months after study initiation
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Queensway Carleton Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto - St. Michael's Hospital
state: Ontario
city: Levis
country: Canada
facility: Hotel Dieu de Levis
state: Quebec
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Quebec City
country: Canada
facility: Hopital de l'Enfant Jesus
state: Quebec
city: Ste-Foy
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec
state: Quebec
Study officials:
affiliation: Unity Health Toronto - St. Michael's Hospital
name: Karen Burns, MD PhD FRCSC
role: PRINCIPAL_INVESTIGATOR
References: