Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study

E. C. Haley, N. F. Kassell, W. M. Alves, B. K.A. Weir, C. A. Hansen, K. Petruk, D. Steinke, D. Schindel, F. E. Leblanc, B. Tranmer, M. Robertson, J. L. Caron -, L. Wadup, M. West, B. Anderson, D. Gladish, G. Mohr, M. Bisset, M. Bouthilier

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Tirilazad mesylate, a 21-aminosteroid free-radical scavenger, has been shown to ameliorate cerebral vasospasm and reduce infarct size in animal models of subarachnoid hemorrhage (SAH) and focal cerebral ischemia. In preparation for performing large-scale clinical trials in humans with aneurysmal SAH, the safety of varying doses of tirilazad was tested in a randomized, double-blind, vehicle-controlled, sequential dose-escalation study at 12 Canadian neurosurgical centers. Two hundred forty-five patients with an aneurysmal SAH documented by angiography were enrolled in the study sequentially within 72 hours of hemorrhage. The patients were assigned to one of three dosage tiers: receiving 0.6 mg/kg, 2 mg/kg, or 6 mg/kg tirilazad or vehicle per day intravenously in divided doses through Day 10 following the SAH. All patients also received oral nimodipine. No serious side effects of tirilazad treatment were identified at any of the three doses, despite close monitoring of hepatic and cardiac toxicity. A trend toward improvement in overall 3-month patient outcome was seen in the 2 mg/kg per day tirilazad treated group compared to the outcomes in the vehicle-treated groups. We conclude that tirilazad mesylate is safe in SAH patients at doses up to 6 mg/kg per day for up to 10 days and is a promising drug for the treatment of patients with aneurysmal SAH.

Original languageEnglish (US)
Pages (from-to)786-790
Number of pages5
JournalJournal of neurosurgery
Issue number5
StatePublished - 1995
Externally publishedYes


  • cerebral aneurysm
  • cerebral ischemia
  • cerebral vasospasm
  • free radical scavengers
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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