Dexanabinol (HU-211) in the treatment of severe closed head injury: A randomized, placebo-controlled, phase II clinical trial

Objective: To establish the safety of intravenous dexanabinol in severe head injury. Design: Prospective, randomized, double-blind, placebo- (vehicle) controlled, multicenter, escalating dose study of a single administration of drug (48 or 150 mg) or vehicle (1 or 3 mL). Setting: All Israeli neurosurgical intensive care units (a total of six units). Patients: Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment. Measurements and Main Results: Intracranial pressure, cerebral perfusion pressure, blood pressure, and heart rate were measured continuously in the intensive care unit. Adverse medical events were recorded and clinical outcome was assessed by the Glasgow outcome scale throughout a 6-month follow-up period. A highly significant reduction in the percentage of time with intracranial pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm Hg was observed in the drug-treated group. The nature and incidence of adverse medical events were similar in the two groups. The percentage of patients achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14% higher in the drug-treated group at 3 and 6 months, respectively. Statistical analysis of these differences by a logistic model using dose, entry Glasgow coma scale score, and computed tomograph as covariates yielded p values for the effect of treatment of .03 and .14 at 3 and 6 months, respectively. Conclusions: Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.