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


CONCLUSIONS
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.
Shibuya
Masato
M
Chukyo Hospital, Nagoya, Japan.
Hirai
Shunsaku
S
Seto
Minoru
M
Satoh
Shin-ichi
S
Ohtomo
Eiichi
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020767:Intracranial Thrombosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil