TREATMENT OF ACUTE ISCHEMIC STROKE WITH PIRACETAM

Background and Purpose Piracetam, a nootropic agent with neuroprotecti ve properties, has been reported in pilot studies to increase compromi sed regional cerebral blood flow in patients with acute stroke and, gi ven soon after onset, to improve clinical outcome. We performed a mult icenter, randomized, double-blind trial to test whether piracetam conf erred benefit when given within 12 hours of the onset of acute ischemi c stroke to a large group of patients. Methods Patients received place bo or 12 g piracetam as an initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g daily for 8 weeks. The primary end point was neurolog ic outcome after 4 weeks as assessed by the Orgogozo scale. Functional status at 12 weeks as measured by the Barthel Index was the major sec ondary outcome. CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment. Analyses based on the int ention to treat were performed in all randomized patients (n = 927) an d in an ''early treatment'' population specified in the protocol as tr eatment within 6 hours of the onset of stroke but subsequently redefin ed as less than 7 hours after onset (n = 452). Results In the total po pulation, outcome was similar with both treatments (the mean Orgogozo scale after 4 weeks: piracetam 57.7, placebo 57.6; the mean Barthel In dex after 12 weeks: piracetam 55.8, placebo 53.1). Mortality at 12 wee ks was 23.9% (111/464) in the piracetam group and 19.2% (89/463) in th e placebo group (relative risk 1.24, 95% confidence interval, 0.97 to 1.59; P = .15). Deaths were fewer in the piracetam group in those pati ents in the intention-to-treat population admitted with primary hemorr hagic stroke. Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo s cale scores after 4 weeks (piracetam 60.4, placebo 54.9; P = .07) and Barthel Index scores at 12 weeks (piracetam 58.6, placebo 49.4; P = .0 2). Additional analyses within this subgroup, confined to 360 patients with moderate and severe stroke (initial Orgogozo scale score < 55), showed significant improvement on piracetam in both outcomes (P < .02) . Conclusions Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Post hoc analyses sugges t that piracetam may confer benefit when given within 7 hours of onset , particularly in patients with stroke of moderate and severe degree. A randomized, placebo-controlled, multicenter study, the Piracetam Acu te Stroke Study II (PASS II) will soon begin.