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).
Level 2 - randomized trial
Predefined tertiary analysis of a randomized, double-blind, placebo-controlled trial
PubMed 27758945 · doi:10.1161/STROKEAHA.116.014672
What was done
This was a predefined tertiary analysis of the URICO-ICTUS double-blind, placebo-controlled phase 2b trial. A total of 411 acute ischemic stroke patients treated with alteplase within 4.5 hours of onset were randomized 1:1 to receive intravenous uric acid 1000 mg (n=211) or placebo (n=200) before completion of the alteplase infusion. The primary outcome for this analysis was early ischemic worsening (EIW), defined as an increment of ≥4 points on the NIH Stroke Scale within 72 hours without hemorrhage or recurrent stroke. Logistic regression was used to assess the interaction between treatment and collateral circulation status in 112 patients with baseline computed tomographic angiography.
What was found
EIW occurred in 7 of 204 (3%) patients receiving uric acid compared to 18 of 200 (9%) receiving placebo (χ²; P=0.01). Overall, EIW was associated with clinical outcome (present in 2 of 149 [1%] patients with good outcome vs. 23 of 262 [9%] with poor outcome; P=0.002). There was a significant interaction between uric acid efficacy and collateral circulation (P=0.029): among patients with good collaterals, EIW occurred in 2% of the uric acid group versus 15% of the placebo group (P=0.048).
Why it matters
These findings provide clinical trial evidence that neuroprotective therapy with uric acid combined with thrombolysis may reduce early neurological worsening, particularly when intact collateral vessels facilitate drug delivery to target ischemic tissue.
Limits
The study is a tertiary analysis of a phase 2b trial rather than a primary trial outcome. The CT angiography collateral evaluation was limited to a subgroup of 112 patients. The findings apply only to patients receiving alteplase within 4.5 hours and require validation in a definitive phase 3 trial.
Cited by
- supports Clinical studies in Spain have investigated intravenous uric acid infusion acutely in stroke patients and suggested potential acute benefits.