Therapeutic Trial of Cerebral Vasospasm with the Serine Protease Inhibitor, FUT-175, Administered in the Acute Stage after Subarachnoid Hemorrhage

The therapeutic effect of the synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. Twenty-three patients with severe SAH who were admitted between February and July 1990 and who underwent surgery within 48 hours of the initial aneurysmal rupture were treated with an intravenous administration of FUT-175 soon after the operation. The patients were divided randomly into three groups, each receiving a different dose of FUT-175 (Group A, 20 mg every 12 hours for 4 days; Group B, 20 mg every 6 hours for 4 days, Group C, 40 mg every 6 hours for 4 days). The results were compared with another group of twenty-two patients with severe SAH who were admitted before February 1990 and received equivalent treatment, except they were not treated with FUT-175. In 64% of all the patients treated with FUT-175 (Groups A, B, C), and in 85% of those treated with higher doses of FUT-175 (Groups B and C), there was no spasm or only mild vasospasm on the angiogram. The incidence of a delayed ischemic neurological deficit significantly decreased from 55% in the control group to 13% in all patients treated with FUT-175 and to 7% in the patients treated with higher doses (P < 0.05). The incidence of cerebral infarction resulting from vasospasm significantly decreased from 43% in the control group to 9% in patients treated with FUT-175. In the patients treated with higher doses of FUT-175 (Groups B and C), none developed cerebral infarction. The outcome 1 month after SAH also significantly improved in patients treated with FUT-175. The patients with a good outcome accounted for 67% of the patients treated with FUT-175, as compared with 35% in the control group. The patients with a poor outcome accounted for only 9% of patients treated with FUT-175, as compared with 36% in the control group. These figures were much more satisfactory in the patients treated with higher doses of FUT-175, i.e., 71% of the patients had a good outcome and none had a poor outcome. FUT-175 is a promising drug for preventing cerebral vasospasm and delayed ischemic neurological deficit after SAH. Additional controlled studies with larger numbers of patients are necessary.