A Pilot Study of Dual Treatment With Recombinant Tissue Plasminogen Activator and Uric Acid in Acute Ischemic Stroke

Abstract

Uric acid (UA) increases the neuroprotective effects of recombinant tissue plasminogen activator (rt-PA) in experimental ischemia. In patients with stroke, increased UA levels have been linked to better stroke recovery, but the clinical safety of dual administration of UA and rt-PA is unknown. Using a double-blind design, we assessed the safety of exogenous UA in patients with acute stroke treated with rt-PA. Patients were randomized to an intravenous solution of 500 mL of 5% mannitol/0.1% lithium carbonate (vehicle group, n=8) or 500 or 1000 mg of UA (n=16). Safety end points at day 90, lipid peroxidation (serum malondialdehyde), and serum kinetics of UA were established. Twenty-four patients with stroke were treated with rt-PA within mean (SD) 133 (35) minutes of clinical onset (admission National Institutes of Health Stroke Scale score mean [SD] 11 [7], age 71 [10.6] years, 71% males). Levels of UA decreased in the vehicle group and increased for approximately 24 hours in the high dose of UA group, which also had lower levels of malondialdehyde at day 5. Mortality (12.5%), symptomatic central nervous system bleeding (0%), and outcome at day 90 were similar in the 3 treatment arms; one patient in the high-dose group had a mild gouty episode. The administration of UA appears to be safe, decreases lipid peroxidation, and prevents an early fall of UA in serum in patients treated with rt-PA within 3 hours of stroke onset. The clinical efficacy of dual administration of exogenous UA and rt-PA deserves further investigation in a larger acute stroke trial.