Clinical trial NCT03143751: Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate to Severe Traumatic Brain Injury
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2017-05-08
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Mortality rate in ICU
timeFrame: 3 months
measure: Mortality rate in ICU
timeFrame: 6 months
measure: GOS-E
timeFrame: 3 months
measure: functional independence measure : ADL (Activities of Daily Living) of Katz
timeFrame: 3 months
measure: functional independence measure : ADL (Activities of Daily Living) of Katz
timeFrame: 6 months
measure: Short Form 36
timeFrame: 3 months
measure: Short Form 36
timeFrame: 6 months
measure: Rate of patients with anterograde amnesia
timeFrame: 3 months
measure: Rate of patients with anterograde amnesia
timeFrame: 6 months
measure: Intracranial pressure control
timeFrame: 7 Days
measure: Blood level of sodium
timeFrame: 7 Days
measure: blood osmolality
timeFrame: 7 Days
measure: Rate of thrombo-embolic events
timeFrame: 28 days
measure: Rate of acute kidney injury
timeFrame: 28 days
measure: Rate of centropontine myelinolysis
timeFrame: 28 days
measure: Blood level of chlore
timeFrame: 7 Days
measure: Blood level of potassium
timeFrame: 5 Days
measure: Blood level of pH (Hydrogen Potention)
timeFrame: 5 Days
measure: brain oxygenation (PtiO2)
timeFrame: 5 Days
measure: blood level of creatinine
timeFrame: 5 Days
measure: Diuresis
timeFrame: 5 Days
measure: weight
timeFrame: 5 Days
measure: Ancillary study: questionnaire HADS (Hospital Anxiety and Depression Scale) in patient's relative
timeFrame: 6 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHU Brest Hopital La Cavale Blanche
city: Clichy
country: France
facility: AP-HP Beaujon
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Centre Hospitalier Sainte-Anne
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes-Hopital Pontchaillou
city: Toulouse
country: France
facility: CHU Toulouse Hôpital Pierre-Paul Riquet
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: CHU de Brest
name: Olivier Huet, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Angers
name: Lasocki Sigismond, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Toulouse
name: Thomas Geerraerts, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Tours
name: Francis Remerand, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Philippe Seguin, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Poitiers
name: Claire Dahyot, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Montpellier
name: Pierre François Perrigault, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP Beaujon
name: Jean Denis Moyer, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP Saint-Anne
name: Tarek SHARSHAR, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roquilly A, Moyer JD, Huet O, Lasocki S, Cohen B, Dahyot-Fizelier C, Chalard K, Seguin P, Jeantrelle C, Vermeersch V, Gaillard T, Cinotti R, Demeure Dit Latte D, Mahe PJ, Vourc'h M, Martin FP, Chopin A, Lerebourg C, Flet L, Chiffoleau A, Feuillet F, Asehnoune K; Atlanrea Study Group and the Societe Francaise d'Anesthesie Reanimation (SFAR) Research Network. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial. JAMA. 2021 May 25;325(20):2056-2066. doi: 10.1001/jama.2021.5561.
citation: Roquilly A, Lasocki S, Moyer JD, Huet O, Perrigault PF, Dahyot-Fizelier C, Seguin P, Sharshar T, Geeraerts T, Remerand F, Feuillet F, Asehnoune K; COBI group. COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome. BMJ Open. 2017 Sep 24;7(9):e018035. doi: 10.1136/bmjopen-2017-018035.