Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. Researchers have assessed whether uric acid therapy would improve functional outcomes at 90 days in patients with acute ischaemic stroke.
URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received Alteplase ( rtPA; Activase ) within 4.5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale ( NIHSS ) score ( greater than 6 and less than or equal to 25 ) and premorbid ( assessed by anamnesis ) modified Rankin Scale ( mRS ) score ( less than or equal to 2 ).
Patients were randomly allocated ( 1:1 ) to receive Uric acid 1000 mg or placebo ( both infused intravenously in 90 min during the infusion of Alteplase ), stratified by centre and baseline stroke severity.
The primary outcome was the proportion of patients with excellent outcome ( ie, an mRS score of 0-1, or 2 if premorbid score was 2 ) at 90 days, analysed in the target population ( all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication ).
During the period 2011-2013, researchers have randomly assigned 421 patients, of whom 411 ( 98% ) were included in the target population ( 211 received Uric acid and 200 received placebo ).
83 ( 39% ) patients who received uric acid and 66 ( 33% ) patients who received placebo had an excellent outcome ( adjusted risk ratio, aOR=1.23; p=0.099 ).
No clinically relevant or statistically significant differences were reported between groups with respect to death ( 28 [ 13% ] patients who received uric acid vs 31 [ 16% ] who received placebo ), symptomatic intracerebral haemorrhage ( 9 [ 4% ] vs 6 [ 3% ] ), and gouty arthritis ( 1 [ less than 1% ] vs 4 [ 2% ] ).
516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 ( 12% ) and 67 ( 13% ), respectively, were serious adverse events ( p=0.703 ).
In conclusion, the addition of Uric acid to thrombolytic therapy did not increase the proportion of patients who achieved excellent outcome after stroke compared with placebo, but it did not lead to any safety concerns. ( Xagena )
Chamorro A et al, The Lancet Neurology 2014; 13: 453-460