Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 282; no. 21; pp. 2003 - 2011
• Main Authors: Furlan, Anthony, Higashida, Randall, Wechsler, Lawrence, Gent, Michael, Rowley, Howard, Kase, Carlos, Pessin, Michael, Ahuja, Arvind, Callahan, Fred, Clark, Wayne M, Silver, Frank, Rivera, Frank, for the PROACT Investigators
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.12.1999
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Clinical outcomes; Drug therapy; Medical procedures; Medical sciences; Pharmacology. Drug treatments; Stroke; Human; Nervous system diseases; Stroke; Enzyme; Acute; Multicenter study; Cardiovascular disease; Controlled therapeutic trial; Cerebral disorder; Vascular disease; Chemotherapy; Randomization; Alteplase; Treatment; Central nervous system disease; Intraarterial administration; Cerebrovascular disease; Fibrinolytic
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.282.21.2003

CONTEXT 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. DESIGN 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. SETTING Fifty-four centers in the United States and Canada. PATIENTS 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. INTERVENTION Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). MAIN OUTCOME MEASURES 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). CONCLUSION 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.