Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 24703208 · doi:10.1016/S1474-4422(14)70054-7
What was done
A randomized, double-blind, placebo-controlled phase 2b/3 trial (URICO-ICTUS) conducted across ten Spanish stroke centers evaluated intravenous uric acid as an adjunct to thrombolysis. Patients aged 18 years or older with acute ischemic stroke (NIHSS 6–25, premorbid mRS ≤2) receiving alteplase within 4.5 hours of symptom onset were randomized 1:1 to receive uric acid (1000 mg infused over 90 minutes) or placebo. The primary outcome was the proportion of patients achieving an excellent outcome (mRS 0–1, or 2 if premorbid score was 2) at 90 days in the target population.
What was found
Of 421 randomized patients, 411 were analyzed (211 uric acid, 200 placebo). Excellent outcome occurred in 39% (83/211) of the uric acid group compared with 33% (66/200) of the placebo group (adjusted RR 1.23, 95% CI 0.96–1.56; p=0.099). No significant differences were observed for mortality (13% [28/211] vs 16% [31/200]), symptomatic intracerebral hemorrhage (4% [9/211] vs 3% [6/200]), or gouty arthritis (<1% [1/211] vs 2% [4/200]). Serious adverse events occurred in 12% (61/516) of uric acid events versus 13% (67/532) of placebo events (p=0.703).
Why it matters
Despite strong preclinical evidence for uric acid's antioxidant neuroprotection, the trial did not demonstrate a statistically significant functional benefit when added to standard thrombolysis, though it proved safe.
Limits
The study was potentially underpowered to detect smaller clinical improvements given the wide confidence interval (RR 0.96–1.56). Findings are restricted to patients receiving alteplase within 4.5 hours and may not generalize to non-thrombolyzed patients or those undergoing endovascular thrombectomy.
Cited by
- supports Clinical studies in Spain have investigated intravenous uric acid infusion acutely in stroke patients and suggested potential acute benefits.