A PHASE-II CLINICAL-TRIAL OF RECOMBINANT HUMAN TISSUE-TYPE PLASMINOGEN-ACTIVATOR AGAINST CEREBRAL VASOSPASM AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

THE RESULTS OF a Phase II clinical trial of intrathecal recombinant ti ssue-type plasminogen activator for the prevention of vasospasm were r eported. The subjects were 53 patients with aneurysmal subarachnoid he morrhage (SAH), Groups 2 to 4 in Fisher's preoperative computed tomogr aphy classification and Grades II to IV in the Hunt-Kosnik classificat ion. Twenty-four hours after surgery, tissue-type plasminogen activato r (TD-2061) was intracisternally administered via a catheter (0.1, 0.2 , or 0.4 mg, three times daily for 5 days). The clot-dissolving effect s assessed as ''effective'' and ''markedly effective'' were virtually the same in the 0.1- and 0.2-mg groups (66.7% and 64.3%, respectively) but slightly lower (53.3%) in the 0.4-mg group, suggesting an adequat e effect in the 0.1- and 0.2-mg groups. Severe angiographic vasospasm was not observed in any of three groups. No intergroup differences wer e noted in the incidence of symptomatic vasospasm, low density on comp uted tomography 1 month after SAH, and functional prognosis. Bleeding complications were noted in 4 patients (7.5%), including 1 case of SAH in the low 0.1 -mg group, 2 cases of SAH in the 0.2-mg group, and 1 c ase of epidural hematoma in the 0.4-mg group. In overall safety rating , 3 cases with increased SAH and 1 case of epidural hematoma were asse ssed as ''safety doubtful.'' Other minor side effects such as headache and hepatic dysfunction attributed to the effect of other simultaneou sly used drugs were assessed as ''almost safe,'' and the rate of ''alm ost safe'' and ''better'' for all dose groups was about 90%, suggestin g a safe dose level for all groups. These results suggest that repeate d intrathecal administration of tissue-type plasminogen activator is u seful for preventing vasospasm even in the low dose of 0.1 mg.