Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients

Phase 3

Completed

• Conditions: Moderate to Severe Traumatic Brain Injury
• Interventions: Drug: NaCl20% (Continuous hyperosmolar therapy)

• Registration Number: NCT03143751
• Lead Sponsor: 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?

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-04-28
• Study First Submitted QC: 2017-05-04
• Study First Posted: 2017-05-08
• Study Start: 2017-10-31
• Primary Completion: 2020-03-05
• Study Completion: 2020-03-05
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-04
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 370

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Continuous hyperosmolar therapy	NaCl20% (Continuous hyperosmolar therapy)	Standard cares plus continuous hyperosmolar therapy (NaCl20%)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (10)

CHU Angers; 🇫🇷 Angers, France

CHU Brest Hopital La Cavale Blanche; 🇫🇷 Brest, France

AP-HP Beaujon; 🇫🇷 Clichy, France

CHU Montpellier; 🇫🇷 Montpellier, France

CHU de Nantes; 🇫🇷 Nantes, France

Centre Hospitalier Sainte-Anne; 🇫🇷 Paris, France

CHU Rennes-Hopital Pontchaillou; 🇫🇷 Rennes, France

CHU Poitiers; 🇫🇷 Poitiers, France

CHU Toulouse Hôpital Pierre-Paul Riquet; 🇫🇷 Toulouse, France

CHU Tours; 🇫🇷 Tours, France