To evaluate the efficacy and safety of
defibrase in patients with acute
cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial.
METHODS: RESULTS: A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive
defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index > or = 95) in
defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P < 0.01), and the proportion of dependent functional status (Barthel Index < or = 60) was a little lower in
defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of
stroke onset. Patients in
defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P < 0.05). Recurrence rate of
stroke at 1 year was lower in the
defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in
defibrase group had higher risk of extracranial
bleeding events (4.7% vs. 1.5%, P < 0.01) and a tendency of higher risk of symptomatic
intracranial hemorrhage. The
hemorrhage incidence was higher in patients with
fibrinogen level < 130 mg/dL than > or = 130 mg/dL (10.6% vs. 3.8%, P < 0.05). Mortality rate at 3 months were slightly higher in
defibrase group than placebo group (5.9% vs. 4.2%).
CONCLUSIONS: The
defibrase is effective to improve neurological function and function of daily living for patients with acute
cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute
cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial
hemorrhage during
defibrase administration were related to the plasma
fibrinogen level.