Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.
BACKGROUND
Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.


OBJECTIVE
To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.


METHODS
PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.


METHODS
Fifty-four centers in the United States and Canada.


METHODS
A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.


METHODS
Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).


METHODS
The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.


RESULTS
For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).


CONCLUSIONS
Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.
Furlan
A
A
Cerebrovascular Center, Department of Neurology, Cleveland Clinic Foundation, Ohio 44195, USA. furlana@ccf.org
Higashida
R
R
Wechsler
L
L
Gent
M
M
Rowley
H
H
Kase
C
C
Pessin
M
M
Ahuja
A
A
Callahan
F
F
Clark
W M
WM
Silver
F
F
Rivera
F
F
D000368:Aged; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002533:Cerebral Angiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D020300:Intracranial Hemorrhages; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012720:Severity of Illness Index; D016019:Survival Analysis; D015912:Thrombolytic Therapy; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase