Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial.
BACKGROUND
Traumatic brain injury is a major cause of death and disability. We sought to assess the safety and efficacy of dexanabinol, a synthetic cannabinoid analogue devoid of psychotropic activity, in severe traumatic brain injury.


METHODS
861 patients with severe traumatic brain injury admitted to 86 specialist centres from 15 countries were included in a multi-centre, placebo-controlled, phase III trial. Patients were randomised to receive a single intravenous 150 mg dose of dexanabinol or placebo within 6 h of injury. The primary outcome was the extended Glasgow outcome scale assessed at 6 months, with the point of dichotomisation into unfavourable versus favourable outcome differentiated by baseline prognostic risk. Prespecified subgroup analyses were defined by injury severity, recruitment rate, and time to dosing. Secondary analysis included control of intracranial pressure and quality of life. Analysis were prespecified in the protocol and the statistical analysis plan. This study is registered with ClinicalTrials.gov, number NCT00129857.


RESULTS
846 patients were included in the efficacy analysis. The extended Glasgow outcome scale at 6 months did not differ between groups; 215 (50%) patients in the dexanabinol group and 214 (51%) patients in the placebo group had an unfavourable outcome (odds ratio for a favourable response 1.04; 95% CI 0.79-1.36). Improvements in the control of intracranial pressure or quality of life were not recorded and subgroup analysis showed no indication of differential treatment effects. Dexanabinol was not associated with hepatic, renal, or cardiac toxic effects.


CONCLUSIONS
Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury.
Maas
Andrew I R
AI
Department of Neurosurgery, Erasmus MC Rotterdam, Rotterdam, Netherlands. airmaas@erasmusmc.nl
Murray
Gordon
G
Henney
Herbert
H
Kassem
Nadim
N
Legrand
Valerie
V
Mangelus
Miriam
M
Muizelaar
Jan-Paul
JP
Stocchetti
Nino
N
Knoller
Nachshon
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale / Q000706:statistics & numerical data; D006801:Humans; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016017:Odds Ratio; D011788:Quality of Life; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D013759:Dronabinol; C062018:HU 211