Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial.

Abstract

BACKGROUND:

A multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of fasudil, a Rho-kinase inhibitor (RKI), in the treatment of acute ischemic stroke.

METHODS:

A total of 160 patients, who were able to receive drug treatment within 48 h of acute ischemic stroke onset were enrolled. Patients received either 60 mg fasudil or a placebo (saline) by intravenous injection over 60 min, twice daily for 14 days. The primary end points were neurological status at 2 weeks after the start of treatment, and clinical outcome at 1 month after the onset of symptoms.

RESULTS:

Fasudil treatment resulted in significantly greater improvements in both neurological functions (p=0.0013), and clinical outcome (p=0.0015). There were no serious adverse events reported in the fasudil group. The average trough value (12 h values) of active metabolite hydroxyfasudil, another RKI, in healthy elderly volunteers receiving 60 mg of fasudil was 0.077 microM-a concentration well above that needed to inhibit Rho-kinase (0.025-0.05 microM).

CONCLUSION:

Treatment with fasudil within 48 h of acute ischemic stroke onset significantly improved the patient's clinical outcome. This study found fasudil to be a useful and safe drug for patients with acute ischemic stroke. Further evaluations, for example, 3-month functional outcomes in a larger clinical trial, may help to define the efficacy of fasudil in acute ischemic stroke.

• Authors: Masato Shibuya, Shunsaku Hirai, Minoru Seto, Shin-ichi Satoh, Eiichi Ohtomo, Fasudil Ischemic Stroke Study Group
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 238 Issue 1-2 Pg. 31-9 (Nov 15 2005) ISSN: 0022-510X [Print] Netherlands
• PMID: 16005902 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Vasodilator Agents
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Protein Serine-Threonine Kinases
• rho-Associated Kinases
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Acute Disease
• Aged
• Brain Ischemia (diagnosis)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Intracellular Signaling Peptides and Proteins
• Intracranial Thrombosis (drug therapy)
• Male
• Middle Aged
• Neurologic Examination
• Prospective Studies
• Protein Serine-Threonine Kinases (metabolism)
• Stroke (drug therapy)
• Vasodilator Agents (adverse effects, pharmacokinetics, therapeutic use)
• rho-Associated Kinases