[Preliminary clinical trial of intrathecal rt-PA (TD-2061) for the prevention of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage].

The results of preliminary clinical trial (a multicenter, open-label, dose escalation study) of intrathecal recombinant tissue plasminogen activator (rt-PA) for the prevention of cerebral vasospasm were reported. Seventeen patients admitted within 48 hours of subarachnoid hemorrhage (SAH) were enrolled in this study. Patients ranged from 42 to 69 years of age. All cases enrolled were classified in clinical grade II, III or IV according to the classification of Hunt and Kosnik and in group 3 or 4 according to Fisher's CT grading scale. Surgery for clipping the aneurysms were performed and a small silicone catheter was left in the subarachnoid space. Twenty four hours after the surgery intrathecal bolus infusion of rt-PA was started through the silicone catheter at 6-hour intervals for 3 days. Patients were divided into 4 groups based on the dosage of rt-PA for each infusion. The dosage of rt-PA for each infusion and a number of cases in each group was as follows; 25 KIU in 4 cases, 75 KIU in 6 cases, 200 KIU in 4 cases and 600 KIU in 3 cases. There was no significant difference in the clearance of subarachnoid clots between four groups. However, the occurrence of both symptomatic and angiographic vasospasm was less in the 75 KIU group than in other three groups. Intracranial bleeding complications were noted in 4 patients (1/6 in the 75 KIU group, 2/4 in the 200 KIU group and 1/3 in the 600 KIU group). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Disorientation was noted in 2 out of 3 patients of the 600 KIU group.(ABSTRACT TRUNCATED AT 250 WORDS)