Brain-injured Patients Extubation Readiness Study (Biper)

Stepped Wedge Cluster Randomised Controlled Trial to Assess the Readiness of Extubation in Brain-injured Patients Using a Clinical Score

The BIPER study is a stepped wedge cluster randomised clinical trial aiming to decrease extubation failure in critically-ill brain-injured patients with residual impaired consciousness using a simple clinical score.

Study Overview

• Status: Recruiting
• Conditions: Acute Brain Injury; Mechanical Ventilation; Altered Level of Consciousness; Mechanical Ventilator Weaning; Airway Control
• Intervention / Treatment: Procedure: Usual Care; Procedure: Extubation readiness clinical score

Detailed Description

Severe brain-injured patients need mechanical ventilation with tracheal intubation. After treatment of the acute neurological condition, weaning of the mechanical ventilation has to be initiated notably to prevent ventilator associated pneumonia and others complications. Nevertheless, extubation failure is very common in this population due to residual neurological impairment with airway control alteration.

Guidelines about weaning of mechanical ventilation and extubation exclude brain-injured patients with a residual impaired consciousness.

In 2017, a simple and pragmatic extubation readiness clinical score was validated in a prospective observational cohort study of 140 brain injured patients. (Godet et al. Anesthesiology. 2017 Jan;126(1):104-114) In this study, brain injured patients with residual impaired consciousness who succeeded a spontaneous breathing trial were extubated. In multivariate analysis, 4 clinical elements were associated with extubation success. A prediction score was determined using the odds ratio such as followed :

1. Deglutition: 3 points if present
2. Gag reflex: 4 points if present
3. Cough: 4 points if present
4. CRS-R Score, visual item >2, 3 points if present, 1 point if not

For a cut-off value of 9, extubation failure could be predicted with a sensibility of 84%, a specificity of 75%, a positive predictive value of 89% and a negative predictive value of 66%.

In order to participate, brain-injured patients will have to succeed a spontaneous breathing trial and meet all inclusion criteria, including not being able to obey to command with no or minimal sedation. Using a stepped wedge randomisation process with intensive care units as clusters, patients will be weaned and extubated under usual care or using the extubation readiness clinical score.

The authors' hypothesis is that this clinical score will allow physicians to extubate patients at the right time interval and prevent extubation failure in this frail population.

• Study Type: Interventional
• Enrollment (Estimated): 660
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: +33 4 73 754963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • CHU
    • Contact: Sigismond Lasocki
  • Bordeaux, France
    • Recruiting
    • CHU
    • Contact: Hugues De Courson
  • Bourg-en-Bresse, France
    • Terminated
    • CH
  • Caen, France
    • Recruiting
    • CHU
    • Contact: Clément Gakuba
  • Clermont-Ferrand, France
    • Recruiting
    • CHU
    • Contact: Russell Chabanne
  • Grenoble, France
    • Completed
    • CHU
  • La Réunion, France
    • Recruiting
    • CHU
    • Contact: Sophie Kauffmann
  • Lille, France
    • Recruiting
    • CHU
    • Contact: Natalie De Sa
  • Lyon, France
    • Recruiting
    • Hospices civils de Lyon
    • Contact: Florent Gobert
  • Marseille, France
    • Withdrawn
    • APHM
  • Montpellier, France
    • Recruiting
    • CHU
    • Contact: Pierre-François Perrigault
  • Nantes, France
    • Completed
    • CHU
  • Nice, France
    • Terminated
    • Pasteur 2 Hospital - University Hospital
  • Nîmes, France
    • Recruiting
    • CHU
    • Contact: Claire Roger
  • Paris, France
    • Recruiting
    • Fondation Ophtalmologique Adolphe de Rothschild
    • Contact: Nicolas Engrand
  • Poitiers, France
    • Recruiting
    • CHU
    • Contact: Claire Dahyot-Fizelier
  • Rennes, France
    • Recruiting
    • CHU
    • Contact: Yoann Launey
  • Saint-Etienne, France
    • Completed
    • CHU
  • Toulouse, France
    • Recruiting
    • CHU
    • Contact: Thomas Geeraerts
  • Valence, France
    • Terminated
    • CH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute cerebral lesion with a Glasgow Coma Scale <13 needing admission in ICU and mechanical ventilation with tracheal intubation for neurological cause : cerebrovascular stroke either ischemic or hemorrhagic including aneurysmal subarachnoid hemorrhage, traumatic brain injury, anoxo ischemic encephalopathy after cardiac arrest or brain tumour
• Mechanical ventilation more than 48 hours
• 18 to 75 years old
• Neurological stability with no intracranial hypertension with minimal sedation
• Glasgow Coma Scale motor response < 6
• Spontaneous breathing trial succeeded
• First extubation attempt

Exclusion Criteria:

• Posterior cranial fossa lesion
• Admission for status epilepticus or central nervous system infection
• Spinal cord injury (tetraplegia or paraplegia)
• Uncontrolled status epilepticus or uncontrolled central nervous system infection
• Care limitation plan
• Chronic respiratory failure defined as ambulatory oxygen therapy or pressure support ventilation and/or proven COPD and/or ambulatory non-invasive CPAP therapy for sleep apnoea syndrome
• More than 3 failed spontaneous breathing trials
• Significant chest trauma (more than 2 broken ribs / broken sternum / with an indication of open thoracic surgery)
• Surgery planned within 7 days
• Tracheotomy or previous extubation outside of the protocol
• Previous compromised upper airway permeability
• Pregnant or breastfeeding woman
• Adult under the protection of the law or without social assurance system
• Inclusion in another clinical study about mechanical ventilation or weaning

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care; Clinicians decide whether to extubate or not following usual care in their ICU ventilator weaning protocol	Procedure: Usual Care; After treatment of the acute neurological condition, eligibility for a spontaneous breathing trial will be assessed once a day. In the control group, after a successful spontaneous breathing trial in unconscious patients, the extubation will be achieved according to usual care.
Experimental: Extubation readiness clinical score; Clinicians decide whether to extubate or not following the extubation readiness clinical score as part of their ICU ventilator weaning protocol	Procedure: Extubation readiness clinical score; After treatment of the acute neurological condition, eligibility for a spontaneous breathing trial will be assessed once a day. In the intervention group, after a successful spontaneous breathing trial in unconscious patients, the score will be evaluated. If the score is > 9, extubation has to be completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extubation failure	Extubation failure is defined as a need of reintubation or death in the 5 days (120 hours) following extubation	From extubation to Day 5 (120 hours) after extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary outcome measure: time to effective extubation	Time from SBT success (enrollment) to successful liberation from mechanical ventilation, defined as the time point at which a patient is alive and free of invasive ventilatory support for more than 5 days (120 hours)	From enrollment to day 5 (120 hours) after extubation
Invasive mechanical ventilation duration	Period expressed in days during which patients will need invasive mechanical ventilation	From admission to the end of ICU Stay
Non-invasive mechanical ventilation duration	Period expressed in days during which patients will need non-invasive mechanical ventilation	From admission to the end of ICU Stay
Reintubation rate in the first 48 hours	Patients needing reintubation during the first 48h post-extubation	From extubation to Day 2 after extubation (48 hours)
Reintubation rate in ICU	Patients needing reintubation during entire ICU stay	From extubation to the end of ICU Stay
Post extubation nosocomial pneumonia	Post extubation nosocomial pneumonia is defined as a pulmonary infection after extubation that necessitate antibiotic therapy	From extubation to the end of ICU stay
Tracheotomy after extubation	Number of patients that necessitate a tracheotomy after extubation failure	From extubation to the end of ICU Stay
Tracheotomy before extubation	Number of patients that necessitate a tracheotomy after a successful spontaneous breathing trial but before any extubation	From enrollment to the end of ICU Stay
ICU length of stay	ICU length of stay expressed in days	From admission to the end of ICU Stay
Hospital length of stay	Hospital length of stay expressed in days	From admission to the end of Hospital Stay
Mortality in ICU	Deceased patient in each group during ICU stay	From enrollment to the end of the ICU Stay
Mortality at day 28	Deceased patient in each group at day 28	From enrollment to Day 28
Mortality at day 90	Deceased patient in each group at day 90	From enrollment to Day 90
Neurological outcome	Neurological outcome using the Glasgow Outcome Scale Extended	Day 90 after enrollment

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: ANARLF Network; Direction Générale de l'Offre de Soin (DGOS)
• Investigators: Principal Investigator: Carole Ichai, CHU Nice; Principal Investigator: Claire Dahyot-Fizelier, CHU Poitiers; Study Director: Russell Chabanne, University Hospital, Clermont-Ferrand; Principal Investigator: Olivier Vincent, University Hospital, Grenoble; Principal Investigator: Florent Gobert, Hospices civils de Lyon; Principal Investigator: Jérôme Morel, Chu Saint-Etienne; Principal Investigator: Matthieu Jeannot, CH Valence; Principal Investigator: Pierre-François Perrigault, University Hospital, Montpellier; Principal Investigator: Camille Bouisse, CH de BOURG-EN-BRESSE; Principal Investigator: Yoann Launey, Chu Rennes; Principal Investigator: Claire Roger, CHU Nîmes; Principal Investigator: Sigismond Lasocki, University Hospital, Angers; Principal Investigator: Pierre-André Rodié-Talbère, Nantes University Hospital; Principal Investigator: Natalie De Sa, CHU Lille; Principal Investigator: Laurent Petit, CHU Bordeaux - Réanimation Chirurgicale et traumatologique; Principal Investigator: Hugues De Courson, CHU Bordeaux - Réanimation Neurologique; Principal Investigator: Clément Gakuba, CHU Caen Normandie; Principal Investigator: Sophie Kauffmann, CHU de la réunion; Principal Investigator: Thomas Geeraerts, University Hospital, Toulouse; Principal Investigator: Nicolas Engrand, Fondation Ophtalmologique Adolphe de Rothschild

Publications and helpful links

General Publications

• Godet T, Chabanne R, Marin J, Kauffmann S, Futier E, Pereira B, Constantin JM. Extubation Failure in Brain-injured Patients: Risk Factors and Development of a Prediction Score in a Preliminary Prospective Cohort Study. Anesthesiology. 2017 Jan;126(1):104-114. doi: 10.1097/ALN.0000000000001379.
• Chabanne R, Godet T, Andanson B, Borrel P, Astier L, Caumon E, Bourguignon N, Laclautre L, Morand D, De Jong A, Futier E, Constantin JM, Pereira B, Jabaudon M. Prevention of extubation failure in neurocritical care patients with residual disorder of consciousness: the Brain-Injured Patients Extubation Readiness (BIPER) study protocol for a stepped-wedge cluster-randomised controlled trial. BMJ Open. 2025 Jul 13;15(7):e104897. doi: 10.1136/bmjopen-2025-104897.

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2020
• Primary Completion (Estimated): February 13, 2027
• Study Completion (Estimated): October 13, 2027

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Critical care; Traumatic brain injury; Coma; Intensive care units; Anoxic ischemic encephalopathy; Glasgow coma scale
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Ischemia; Signs and Symptoms, Respiratory; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia, Brain; Unconsciousness; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries, Traumatic; Stroke; Brain Injuries; Hypoxia-Ischemia, Brain; Consciousness Disorders; Coma
• Other Study ID Numbers: Biper - PhrcIR 2017 Chabanne; 2018-A00894-51 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing plan : BIPER clinical trial data will be made available upon reasonable request as soon as study publication with deidentified participant data and statistical/analytic code
• IPD Sharing Time Frame: As soon as study publication in a peer review journal with a 5 years limit.
• IPD Sharing Access Criteria: Data will be made available on reasonable demand by emailing the coordinating clinical investigator of the trial. A proposal that describes planned analyses will have to be submitted and a data sharing agreement signed. Requests will be evaluated by the coordinating clinical investigator and study statistician of the trial.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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