The NEUROlogically-impaired Extubation Timing Trial

Study Overview
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Brief Summary
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This randomized controlled trial will enrol patients with acute severe brain injury who pass a spontaneous breathing trial but have decreased level of consciousness. It will directly compare (1) prompt extubation vs. (2) usual care, with extubation or tracheostomy timed according to physicians' discretion. The primary outcome will be ICU free days (days spent alive and outside an ICU).

Detailed Description
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Thousands of patients suffer severe brain injuries every year, from causes such as trauma, stroke, and infection. Extensive clinical research in weaning from mechanical ventilation has led to recommendations for prompt extubation following a successful trial of spontaneous breathing in general intensive care unit (ICU). However, little evidence exists to guide decisions about when to remove the breathing tube in patients with severe brain injury. It is unclear which of the following strategies would optimize important patient outcomes: prompt extubation vs. waiting and extubating or performing a tracheostomy, timed according to physicians' discretion. Each strategy has associated risks: prompt extubation may lead to higher rates of extubation failure and reintubation, whereas waiting longer may expose patients to complications from prolonged mechanical ventilation and tracheostomy may lead to procedural complications (or unnecessary procedures, if prompt extubation would be successful). This trial in brain-injured patients will test which of the following will lead to better patient outcomes: (1) removing the endotracheal tube promptly once a spontaneous breathing trial is passed; or (2) usual care, with the airway management strategy selected according to the preference of the treating physician.

Official Title
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The NEUROlogically-impaired Extubation Timing Trial

Conditions
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Acute Brain Injury

Intervention / Treatment
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* Procedure: Extubation
* Procedure: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 16 years Acute brain injury (subarachnoid hemorrhage, ischemic stroke, spontaneous intracerebral hemorrhage, seizure, traumatic brain injury, brain tumor, global cerebral anoxia/cardiac arrest, meningitis/encephalitis/cerebral abscess) that occurred within the previous 4 weeks. Receiving invasive mechanical ventilation via endotracheal tube for > 72 hours Glasgow Coma Scale motor score 3 to 6 with improvement or no change from previous day passed spontaneous breathing trial (SBT) Exclusion Criteria: Previous extubation during this ICU admission Quadriplegic Neuromuscular disease that will result in prolong need for mechanical ventilation, including but not limited to Guillain-Barre syndrome, cervical spinal cord injury, advanced multiple sclerosis Do-Not-Reintubate order in place Previously randomized in this trial Underlying pre-existing condition with expected mortality less than 6-months. Anticipated/scheduled for surgical procedures within 48 hours C-spine not yet cleared for activity as tolerated (cleared for activity as tolerated while wearing hard collar is acceptable) Currently known or suspected to have an difficult airway Absence of an endotracheal tube cuff leak, if checked Absence of spontaneous or induced cough Current enrolment in an RCT that precludes NEURO-ETT co-enrollment

Ages Eligible for Study
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Minimum Age: 16 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Extubation<br>Extubation by removal of endotracheal tube. | Procedure: Extubation<br>* This is an extubation by removal of endotracheal tube which must be done on the day of randomization or the following day. Any decision to subsequently reintubate the patient will be left to the discretion of the clinical team. Similarly, if a tracheostomy is deemed necessary in a patient who fails the extubation attempt, this will be managed at the discretion of the treating team. If for any reason the patient is not extubated according to the randomized schedule, the reason(s) will be recorded on a protocol violation form and the site investigator will be notified. If a patient receives a tracheostomy instead of being extubated we will again record reasons for this, but the patient will be analysed in the extubation group according to the intention-to-treat principle.<br>|
| Active Comparator: Usual care<br>The usual clinical practice is removal of the endotracheal tube (extubation), or insertion of tracheostomy, timed according to physicians' discretion | Procedure: Usual Care<br>* Patients in this group will be treated according to usual care, which may include extubation (removal of endotracheal tube) or insertion of a tracheostomy, timed according to physicians' discretion. The inclusion of this arm will allow prompt extubation to be compared to usual practice, which often involves further observation and delayed decision-making due to clinician uncertainty about the optimal airway management strategy. Incorporation of usual care arms has been promoted as a design feature to improve the safety and interpretability of critical care clinical trials.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU Free Days | The primary outcome is number of ICU free days to day 60, defined as the number of days spent alive and outside of an ICU until day 60. The primary outcome will be measured to answer the following primary question: Among patients receiving minimal mechanical ventilatory support for severe and persistent brain injury, which of the following airway management strategies increase ICU-free days to day 60: (1) prompt extubation vs. (2) usual care, which may include extubation or tracheostomy timed according to physicians' discretion? | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality, | Mortality at ICU discharge, mortality at hospital discharge, mortality at 3 months, mortality at 6 months | up to 6 months | 
| Ventilator-Free Days | Days free of mechanical ventilation, total duration (days) of ventilation among survivors | up to 60 days | 
| Airway Complications | Presence versus absence of airway complication | up to 60 days | 
| Nutrition Intake | Time to normal oral nutrition intake | up to 6 months | 
| Antibiotic Days | Injection or infusion of antibiotics given intravenously | up to day 14 | 
| Delirium | Presence versus absence of delirium experienced | up to day 14 | 
| Rate of Tracheostomy Insertion | Presence versus absence of tracheostomy insertion | up to 6 months | 
| Rate of ICU Readmission | ICU readmission rates to hospital discharge | up to hospital discharge | 
| Hospital Discharge Destination | Destination of the patient post hospitalization - home, rehabilitation facility, retirement home, long-term care/nursing home, no fixed address or shelter, continuing complex care, acute care hospital, other | at hospital discharge | 
| Extended Glasgow Outcome Score | Functional outcome (scoring 1 to 8) | up to 6 months | 
| EQ-5D | Health related quality of life (scoring 1 to 5) | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subarachnoid hemorrhage, Spontaneous intracerebral hemorrhage, Global cerebral anoxia/cardiac arrest, Meningitis/Encephalitis/Cerebral abscess, Seizure, Traumatic Brain Injury (TBI), Ischemic Stroke, Brain tumor