Uric Acid Therapy Prevents Early Ischemic Stroke Progression: A Tertiary Analysis of the URICO-ICTUS Trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke)

Abstract

Background and purpose: Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation.

Methods: URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography.

Results: EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ²; P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ²; P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048).

Conclusions: UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00860366.

Keywords: antioxidant; clinical trials; ischemic stroke; neuroprotection; treatment.