The NEUROlogically-impaired Extubation Timing Trial (NEURO-ETT)

• ClinicalTrials.gov Identifier: NCT02920580
• Recruitment Status: Active, not recruiting
• First Posted: September 30, 2016
• Last Update Posted: February 5, 2020
• Sponsor: Sunnybrook Health Sciences Centre
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Dr. Damon Scales, Sunnybrook Health Sciences Centre

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Acute Brain Injury	Procedure: Extubation; Procedure: Usual Care	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Health Services Research
• Official Title: The NEUROlogically-impaired Extubation Timing Trial
• Actual Study Start Date: February 1, 2017
• Actual Primary Completion Date: June 19, 2019
• Estimated Study Completion Date: January 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Extubation; Extubation by removal of endotracheal tube.	Procedure: Extubation; 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.
Active Comparator: Usual care; The usual clinical practice is removal of the endotracheal tube (extubation), or insertion of tracheostomy, timed according to physicians' discretion	Procedure: Usual Care; 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.

Outcome Measures

Primary Outcome Measures :

1. ICU Free Days [ Time Frame: 60 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?

Secondary Outcome Measures :

1. Mortality, [ Time Frame: up to 6 months ]
   Mortality at ICU discharge, mortality at hospital discharge, mortality at 3 months, mortality at 6 months
2. Ventilator-Free Days [ Time Frame: up to 60 days ]
   Days free of mechanical ventilation, total duration (days) of ventilation among survivors
3. Airway Complications [ Time Frame: up to 60 days ]
   Presence versus absence of airway complication
4. Nutrition Intake [ Time Frame: up to 6 months ]
   Time to normal oral nutrition intake
5. Antibiotic Days [ Time Frame: up to day 14 ]
   Injection or infusion of antibiotics given intravenously
6. Delirium [ Time Frame: up to day 14 ]
   Presence versus absence of delirium experienced
7. Rate of Tracheostomy Insertion [ Time Frame: up to 6 months ]
   Presence versus absence of tracheostomy insertion
8. Rate of ICU Readmission [ Time Frame: up to hospital discharge ]
   ICU readmission rates to hospital discharge
9. Hospital Discharge Destination [ Time Frame: at hospital discharge ]
   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
10. Extended Glasgow Outcome Score [ Time Frame: up to 6 months ]
    Functional outcome (scoring 1 to 8)
11. EQ-5D [ Time Frame: up to 6 months ]
    Health related quality of life (scoring 1 to 5)

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2B7

Canada, British Columbia

Royal Columbian Hospital

New Westminster, British Columbia, Canada, V3L 3W7

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Ontario

Hamilton General Hospital

Hamilton, Ontario, Canada, L8N 3Z5

Kingston General Hospital

Kingston, Ontario, Canada, K7L 2V7

London Health Sciences Centre

London, Ontario, Canada, N6A 5A5

Ottawa Hospital

Ottawa, Ontario, Canada, K1H 8L6

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Toronto Western Hospital

Toronto, Ontario, Canada, M5G 2N2

Canada, Quebec

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada, H2X 2H8

Hôpital du Sacré-Cœur de Montréal

Montreal, Quebec, Canada, H4J 1C5

L'Hôpital de l'Enfant-Jésus

Quebec City, Quebec, Canada, G1J 1Z4

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Niall Ferguson, MD, MSc,; Toronto General Hospital
• Principal Investigator: Damon Scales, MD, PhD; Sunnybrook Health Sciences Centre

More Information

• Responsible Party: Dr. Damon Scales, MD, PhD, FRCPC, Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT02920580
• Other Study ID Numbers: NEURO-ETT (Vanguard)
• First Posted: September 30, 2016
• Last Update Posted: February 5, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. Damon Scales, Sunnybrook Health Sciences Centre:

Subarachnoid hemorrhage; Spontaneous intracerebral hemorrhage; Global cerebral anoxia/cardiac arrest; Meningitis/Encephalitis/Cerebral abscess; Seizure; Traumatic Brain Injury (TBI); Ischemic Stroke; Brain tumor

Additional relevant MeSH terms:

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries