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.


METHODS
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).


METHODS
All Israeli neurosurgical intensive care units (a total of six units).


METHODS
Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment.


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.
Knoller
Nachshon
N
Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel.
Levi
Leon
L
Shoshan
Igal
I
Reichenthal
Eli
E
Razon
Nissim
N
Rappaport
Zvi H
ZH
Biegon
Anat
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D016489:Head Injuries, Closed / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018709:Statistics, Nonparametric
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211