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Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients (COBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03143751
Recruitment Status : Completed
First Posted : May 8, 2017
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention or the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long term outcomes is uncertain. The aim of the current study is to assess the efficiency and the safety of continuous hyperosmolar therapy in TBI patients.

The COBI trial is the first randomized controlled trial powered to investigate whether continuous hyperosmolar therapy in TBI patients improve long term recovery.

Hypothesis

Patients treated with early continuous hyperosmolar therapy have reduced morbidity and mortality rates compared to those receiving standard care alone after traumatic brain injury.

Research Questions

  1. Does early continuous hyperosmolar therapy reduce morbidity and mortality rates at 3 and 6 months after TBI assessed by the GOSE questionnaire?
  2. Does early continuous hyperosmolar therapy prevent intracranial hypertension?

Condition or disease Intervention/treatment Phase
Moderate to Severe Traumatic Brain Injury Drug: NaCl20% (Continuous hyperosmolar therapy) Phase 3

Detailed Description:

Background Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI.

Continuous infusion of hyperosmolar therapy has been proposed for the prevention or the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long term outcomes is uncertain. The aim of the current study is to assess the efficiency and the safety of continuous hyperosmolar therapy in TBI patients.

Methods The COBI (Continuous hyperosmolar therapy in traumatic brain-injured patients) trial is a multicenter, randomized, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalized in Intensive Care Unit with a traumatic brain injury (Glasgow Coma Scale ≤ 12 and abnormal brain CT-scan) are randomized in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (NaCl 20%) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent intracranial hypertension. The primary outcome is the score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for pre-specified prognostic factors and expressed as a common odds ratio.

Discussion The COBI trial is the first randomized controlled trial powered to investigate whether continuous hyperosmolar therapy in TBI patients improve long term recovery.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 370 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Masking: Open label , Masked Roles: Subject and Outcomes assessor
Primary Purpose: Treatment
Official Title: Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients Study Protocol for a Multicenter Randomized Open-label Trial With Blinded Adjudication of Primary Outcome
Actual Study Start Date : October 31, 2017
Actual Primary Completion Date : March 5, 2020
Actual Study Completion Date : March 5, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Continuous hyperosmolar therapy
Standard cares plus continuous hyperosmolar therapy (NaCl20%)
Drug: NaCl20% (Continuous hyperosmolar therapy)

Early intravenous administration (<24 hours after traumatic brain injury) of NaCl20% for a minimal duration of 48 hours (continued for as long as is necessary to prevent intracranial hypertension)

1-hour bolus (15 g if Na+ < 145 mmol/L; 7.5 g if 145 < Na+ < 150 mmol/L; or no bolus) followed by 1 g/hour as long as Na+< 150 mmol/L, reduced to 0.5 g/L if 150 < Na+ < 155 mmol/L, Discontinuation when 155 mmol/L<Na+


No Intervention: Control
Standard cares alone.



Primary Outcome Measures :
  1. Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months [ Time Frame: 6 months ]
    The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries


Secondary Outcome Measures :
  1. Mortality rate in ICU [ Time Frame: 3 months ]
  2. Mortality rate in ICU [ Time Frame: 6 months ]
  3. GOS-E [ Time Frame: 3 months ]
    The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries

  4. functional independence measure : ADL (Activities of Daily Living) of Katz [ Time Frame: 3 months ]
    Scale measuring the autonomy of patient

  5. functional independence measure : ADL (Activities of Daily Living) of Katz [ Time Frame: 6 months ]
    Scale measuring the autonomy of patient

  6. Short Form 36 [ Time Frame: 3 months ]
    Scale measuring the quality of life

  7. Short Form 36 [ Time Frame: 6 months ]
    Scale measuring the quality of life

  8. Rate of patients with anterograde amnesia [ Time Frame: 3 months ]
  9. Rate of patients with anterograde amnesia [ Time Frame: 6 months ]
  10. Intracranial pressure control [ Time Frame: 7 Days ]
  11. Blood level of sodium [ Time Frame: 7 Days ]
  12. blood osmolality [ Time Frame: 7 Days ]
  13. Rate of thrombo-embolic events [ Time Frame: 28 days ]
  14. Rate of acute kidney injury [ Time Frame: 28 days ]
    KDIGO 3

  15. Rate of centropontine myelinolysis [ Time Frame: 28 days ]
    Diagnosis on MRI realized in case of clinical suspicion

  16. Blood level of chlore [ Time Frame: 7 Days ]
  17. Blood level of potassium [ Time Frame: 5 Days ]
  18. Blood level of pH (Hydrogen Potention) [ Time Frame: 5 Days ]
  19. brain oxygenation (PtiO2) [ Time Frame: 5 Days ]
  20. blood level of creatinine [ Time Frame: 5 Days ]
  21. Diuresis [ Time Frame: 5 Days ]
  22. weight [ Time Frame: 5 Days ]
  23. Ancillary study: questionnaire HADS (Hospital Anxiety and Depression Scale) in patient's relative [ Time Frame: 6 months ]
    Scale measuring the quality of life



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18-80 years old
  • Moderate to severe traumatic brain injury defined as the association of a Coma Glasgow Scale ≤ 12 together with a traumatic abnormal brain CT-scan
  • Time to inclusion inferior to 24 hours
  • Informed consent (or emergency procedure)

Exclusion Criteria:

  • dependence for daily activity
  • Coma Glasgow Scale of 3 and fixed dilated pupils
  • associated cervical spine injury
  • imminent death and do-not-resuscitate orders
  • pregnancy.
  • Major not legally responsible
  • Oedemato-ascitic decompensation of hepatic cirrhosis
  • State of hydro-sodium retention secondary to heart failure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03143751


Locations
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France
CHU Angers
Angers, France
CHU Brest Hopital La Cavale Blanche
Brest, France, 29600
AP-HP Beaujon
Clichy, France, 92118
CHU Montpellier
Montpellier, France
CHU de Nantes
Nantes, France, 44093
Centre Hospitalier Sainte-Anne
Paris, France, 75014
CHU Poitiers
Poitiers, France, 86000
CHU Rennes-Hopital Pontchaillou
Rennes, France
CHU Toulouse Hôpital Pierre-Paul Riquet
Toulouse, France, 31059
CHU Tours
Tours, France, 37044
Sponsors and Collaborators
Nantes University Hospital
Investigators
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Principal Investigator: Olivier Huet, PU-PH CHU de Brest
Principal Investigator: Lasocki Sigismond, PU-PH University Hospital, Angers
Principal Investigator: Thomas Geerraerts, PU-PH University Hospital, Toulouse
Principal Investigator: Francis Remerand, PU-PH CHU de Tours
Principal Investigator: Philippe Seguin, PU-PH Rennes University Hospital
Principal Investigator: Claire Dahyot, PU-PH CHU Poitiers
Principal Investigator: Pierre François Perrigault, PU-PH University Hospital, Montpellier
Principal Investigator: Jean Denis Moyer, PU-PH AP-HP Beaujon
Principal Investigator: Tarek SHARSHAR, PU-PH AP-HP Saint-Anne
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT03143751    
Other Study ID Numbers: RC16_0474
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries