Clinical study of OKY-046, a thromboxane synthetase inhibitor, in prevention of cerebral vasospasms and delayed cerebral ischaemic symptoms after subarachnoid haemorrhage due to aneurysmal rupture: a randomized double-blind study.
A double-blind study was conducted at 48 neurosurgical services in Japan to investigate the usefulness of OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, on cerebral vasospasm and cerebral ischaemic symptoms in patients with ruptured cerebral aneurysms. OKY-046 was administered in two daily doses of 80 mg (L group) and 400 mg (H group), and compared with a group given a placebo (P group). The following results were obtained: the occurrence of cerebral vasospasm was significantly lower in the L group than in the P group; the development of low density area (LD) in CTs was significantly lower in both the L and H groups than in the P group; motor paralysis in the L group improved significantly sooner, and that in the H group tended to improve sooner than that in the P group; in subjects with severe vasospasm, the incidence of LD was significantly lower, with better functional prognosis, in the L group than in the P group; in subjects with severe grades on the Glasgow Coma Scale (GCS), Japan Coma Scale (JCS) or High Density (HD) Score the functional prognosis at 1 month after the aneurysmal rupture was significantly better in the L group than in the P group, though no significant differences were seen in the overall investigation; there were no significant differences among the three groups in the development of either laboratory-determined abnormality or of adverse reactions. It is thus concluded that OKY-046 is clinically useful at a dose of 80 mg/d for cerebral vasospasm and cerebral ischaemic symptoms after subarachnoid haemorrhage (SAH) caused by aneurysmal rupture.
Suzuki
S
S
Department of Neurosurgery, Hirosaki University School of Medicine, Japan.
Sano
K
K
Handa
H
H
Asano
T
T
Tamura
A
A
Yonekawa
Y
Y
Ono
H
H
Tachibana
N
N
Hanaoka
K
K
D000179:Acrylates / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000792:Angiography; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D002532:Intracranial Aneurysm / Q000150:complications*; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009132:Muscles / Q000503:physiopathology; D010243:Paralysis / Q000503:physiopathology; D011379:Prognosis; D011897:Random Allocation; D012422:Rupture, Spontaneous; D013223:Statistics as Topic; D013345:Subarachnoid Hemorrhage / Q000209:etiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014057:Tomography, X-Ray Computed
D000179:Acrylates; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel