Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients
Condition: Moderate to Severe Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional
Phase: Phase 3

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?
    

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.
    

Intervention name(s): NaCl20% (Continuous hyperosmolar therapy)
Intervention type(s): Drug
Intervention description(s): 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+
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment