Objective: Does hyperosmolar therapy (mannitol or hypertonic saline) in traumatic brain injury (TBI) improve neurological function clinically and cost- effectively at 6 months?
Design: Multi-centre, open label, randomised controlled clinical and cost effectiveness trial with an internal pilot
Setting: Intensive Care Units (ICUs) within NHS hospitals treating patients with TBI
Target population: Adult patients (aged >16 years) with severe TBI and raised intracranial pressure (ICP)
Inclusion criteria: Patients aged ≥16 years old, admitted to ICU following TBI within 10 days from initial primary head injury, abnormal CT scan consistent with TBI and an ICP >20 mmHg for more than 5 mins despite stage 1 procedures
Exclusion criteria: Devastating brain injury with withdrawal of life sustaining treatment anticipated in the next 24 hours, pregnancy and severe hypernatraemia (serum Na > 155 mmol/L)
Planned sample size: 319 per group (638 in total)
Interventions: 2 ml/kg 20% mannitol intravenous bolus and 2 ml/kg 3% hypertonic saline (HTS) intravenous bolus (or equivalent osmolar dose of HTS using the concentration used locally by participating study centres)
Outcome measures:
Primary outcome: Extended Glasgow Outcome Scale (GOS-E) measured at 6 months after randomisation.
Secondary outcome measures: Efficacy – ICP control (during period of monitoring in ICU, progression to stage 3 therapies and requirement for stage 3 therapies to control ICP, Resource use – organ support requirements during ICU, critical care length of stay and hospital length of stay. Patient outcomes – longer term neurological outcomes (Modified Oxford Handicap Scale (mOHS) at discharge and GOS-E at 12 months), Survival (to hospital discharge – defined as the time at which the patient is discharged from the hospital regardless of neurological status, outcome or destination and at 3 months, 6 months and 12 months) and quality of life (EQ-5D-5L at hospital discharge, 3 months, 6 months and 12 months post-TBI)
Blinding: Open label with blinded assessment of primary and secondary outcomes
Follow up period: Up to 12 months post-randomisation
Planned trial period: From 01/06/2019 to 01/12/2023 (total of 54 months)
Trial Registration: ISRCTN16075091
