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.