Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients (COBI)

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

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?

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.

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+

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

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.

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.