Piracetam in the treatment of acute stroke.

The neuroprotective properties of the nootropic agent piracetam together with reported hemorrheologic 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 motor function, aphasia and level of consciousness. Subsequently the Piracetam in Acute Stroke Study (PASS) was performed and the chief results have recently been reported (Stroke 28 (1997) 2347-2352). This was a multicenter double-blind trial in 927 patients to determine whether, compared with placebo, piracetam improved outcome when given within 12 hours of the onset of acute ischemic stroke, confirmed by computed tomography within 24 hours of admission (but not necessarily prior to treatment). Patients received an initial iv bolus of placebo or 12g piracetam, 12g piracetam daily for 4 weeks and maintenance treatment for a further 8 weeks. Neurologic status at 4 weeks was the primary end point; secondary outcome measures were functional outcome and aphasia at 12 weeks. Results in aphasic patients have not previously been reported. Analysis was planned both in all patients (n = 927) and an early treatment subgroup (n = 460) treated within 6 hours of stroke onset. This period was 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 recovered from aphasia but no significant neurologic or functional improvement. Post hoc analysis in the early treatment subgroup showed improved neurologic outcome (P = 0.07), better function (P = 0.02) and a greater recovery rate from aphasia (P = 0.02). Additional analysis in this early treatment subgroup confined to 360 patients with moderate and severe stroke showed significant improvement in all 3 outcomes. There was no significant difference in mortality between treatment groups after 12 weeks. There were fewer deaths in piracetam-treated patients in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke.

RCT Entities:   Population Interventions Outcomes