Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients

Moderate to Severe Traumatic Brain Injury Clinical Trial

— COBI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03143751
• Other study ID #: RC16_0474
• Status: Completed
• Phase: Phase 3
• Start date: October 31, 2017
• Est. completion date: March 5, 2020

Study information

• Verified date: December 2020
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: March 5, 2020
• Est. primary completion date: March 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Moderate to Severe Traumatic Brain Injury

Intervention

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+

Locations

Country	Name	City	State
France	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 Poitiers	Poitiers
France	CHU Rennes-Hopital Pontchaillou	Rennes
France	CHU Toulouse Hôpital Pierre-Paul Riquet	Toulouse
France	CHU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

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