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NCT Number: NCT03143751

Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients

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?

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Key information

Conditions

Moderate to Severe Traumatic Brain Injury

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU Angers, Angers, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NaCl20% (Continuous hyperosmolar therapy)

Drug

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+

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Registry information

Official study title

Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients Study Protocol for a Multicenter Randomized Open-label Trial With Blinded Adjudication of Primary Outcome

Acronym: COBI

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
May 8, 2017
Registry last updated
Dec 8, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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