Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients

Study Overview
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Brief Summary
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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 Does early continuous hyperosmolar therapy reduce morbidity and mortality rates at 3 and 6 months after TBI assessed by the GOSE questionnaire? Does early continuous hyperosmolar therapy prevent intracranial hypertension?

Detailed Description
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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.

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

Conditions
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Moderate to Severe Traumatic Brain Injury

Intervention / Treatment
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* Drug: NaCl20% (Continuous hyperosmolar therapy)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous hyperosmolar therapy<br>Standard cares plus continuous hyperosmolar therapy (NaCl20%) | Drug: NaCl20% (Continuous hyperosmolar therapy)<br>* 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+<br>|
| No Intervention: Control<br>Standard cares alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months | The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate in ICU |  | 3 months | 
| Mortality rate in ICU |  | 6 months | 
| GOS-E | The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries | 3 months | 
| functional independence measure : ADL (Activities of Daily Living) of Katz | Scale measuring the autonomy of patient | 3 months | 
| functional independence measure : ADL (Activities of Daily Living) of Katz | Scale measuring the autonomy of patient | 6 months | 
| Short Form 36 | Scale measuring the quality of life | 3 months | 
| Short Form 36 | Scale measuring the quality of life | 6 months | 
| Rate of patients with anterograde amnesia |  | 3 months | 
| Rate of patients with anterograde amnesia |  | 6 months | 
| Intracranial pressure control |  | 7 Days | 
| Blood level of sodium |  | 7 Days | 
| blood osmolality |  | 7 Days | 
| Rate of thrombo-embolic events |  | 28 days | 
| Rate of acute kidney injury | KDIGO 3 | 28 days | 
| Rate of centropontine myelinolysis | Diagnosis on MRI realized in case of clinical suspicion | 28 days | 
| Blood level of chlore |  | 7 Days | 
| Blood level of potassium |  | 5 Days | 
| Blood level of pH (Hydrogen Potention) |  | 5 Days | 
| brain oxygenation (PtiO2) |  | 5 Days | 
| blood level of creatinine |  | 5 Days | 
| Diuresis |  | 5 Days | 
| weight |  | 5 Days | 
| Ancillary study: questionnaire HADS (Hospital Anxiety and Depression Scale) in patient's relative | Scale measuring the quality of life | 6 months |