Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan.

BACKGROUND AND PURPOSE The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset. METHODS Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index. RESULTS The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level (P=0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P=0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group (P=0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group (P=1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively (P=0.206). CONCLUSIONS The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.