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

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).

Study Overview

• Status: Unknown
• Conditions: Acute Brain Injury
• Intervention / Treatment: Procedure: Extubation; Procedure: Usual Care

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Royal Columbian Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton General Hospital
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto Western Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
    • Montreal, Quebec, Canada, H2X 2H8
      • Centre Hospitalier de l'Universite de Montreal
    • Quebec City, Quebec, Canada, G1J 1Z4
      • L'Hôpital de l'Enfant-Jésus

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Damon Scales, MD, PhD, Sunnybrook Health Sciences Centre; Principal Investigator: Niall Ferguson, MD, MSc,, Toronto General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): June 19, 2019
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (Estimate): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Brain tumor; Ischemic Stroke; Subarachnoid hemorrhage; Seizure; Spontaneous intracerebral hemorrhage; Traumatic Brain Injury (TBI); Global cerebral anoxia/cardiac arrest; Meningitis/Encephalitis/Cerebral abscess
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries
• Other Study ID Numbers: NEURO-ETT (Vanguard)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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