Piracetam in the treatment of acute stroke

The documented neuroprotective properties of the nootropic agent piracetam together with reported haemorrheological and antithrombotic effects provided the rationale for the evaluation of piracetam in acute stroke. Pilot studies showed an increase in compromised regional cerebral blood flow and improvement in functional ability, aphasia and level of consciousness with piracetam. Subsequently, the Piracetam in Acute Stroke Study (PASS) was performed and the principal results have recently been reported. The aim of this multicentre double-blind trial in 927 patients was to determine whether, compared with placebo, piracetam improved outcome when given within 12 hours of the onset of acute ischaemic stroke, confirmed by computed tomography within 24 hours of admission (not necessarily prior to treatment). Patients received an initial intravenous bolus of placebo or piracetam 12g, piracetam 12g daily for 4 weeks and maintenance treatment (4.8g daily) for a further 8 weeks. Neurological status at 4 weeks was the primary end-point; secondary outcome measures were functional out come and aphasia at 12 weeks. Results in patients with aphasia have previously not been reported. Analysis was planned in all patients (n = 927) and in an early treatment subgroup (n = 460), which was treated within 6 hours of stroke onset, a period subsequently redefined as 7 hours. Intention-to-treat analyses in the total population showed a significant (p > 0.04) increase, compared with placebo, in the number of patients who recovered from aphasia, but no significant change in neurological or functional outcome. Post hoc analysis in the early treatment subgroup showed improved neurological outcome (p = 0.07), better functional ability (p = 0.02) and a greater recovery rate from aphasia (p = 0.02). Additional analysis confined to 360 patients with moderate and severe stroke in this early treatment subgroup showed significant improvement in all outcomes. There was no significant difference in mortality between treatment groups after 12 weeks. There were fewer deaths in piracetam-treated patients in the intention-to-treat population admitted with primary haemorrhagic stroke. The PASS confirmed the improvement in aphasia seen in pilot studies with piracetam, and showed an improvement in neurological outcome and better functional ability with piracetam in patients treated within 7 hours of stroke onset, particularly those with moderate and severe stroke. A randomised double-blind trial that aims to prospectively confirm these findings is in progress.