Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial.
BACKGROUND
Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in patients with acute ischaemic stroke.


METHODS
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 within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤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). The study is registered with ClinicalTrials.gov, number NCT00860366.


RESULTS
Between July 1, 2011, and April 30, 2013, we 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 1·23 [95% CI 0·96-1·56]; 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 (nine [4%] vs six [3%]), and gouty arthritis (one [<1%] vs four [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).


CONCLUSIONS
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.


BACKGROUND
Institute of Health Carlos III of the Spanish Ministry of Health and Fundación Doctor Melchor Colet.
Comprehensive Stroke Center, Department of Neuroscience, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain; August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Electronic address: achamorro@clinic.ub.es.
Angel
A
Chamorro
Comprehensive Stroke Center, Department of Neuroscience, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain; August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Sergio
S
Amaro
Department of Neurology, Hospital Universitario Doctor Josep Trueta, Girona, Spain.
Mar
M
Castellanos
Department of Neurology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Tomás
T
Segura
Stroke Unit, Department of Neurology and Medicine, Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain.
Juan
J
Arenillas
Department of Neurology, Hospital de la Santa Creu i Sant Pau (IIb Sant Pau), Barcelona, Spain.
Joan
J
Martí-Fábregas
Department of Neurology, Hospital de Navarra, Pamplona, Spain.
Jaime
J
Gállego
Cerebrovascular Diseases Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Barcelona, Spain.
Jurek
J
Krupinski
Department of Neurosciences, Hospital Universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Barcelona, Spain.
Meritxell
M
Gomis
Neurology Service Corporació Sanitària Parc Taulí, Parc Taulí, Sabadell, Spain.
David
D
Cánovas
Department of Clinical Pharmacology, Unitat d'Avaluació, Suport i Prevenció, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain; August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Xavier
X
Carné
Clinical Biochemistry Laboratory, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain.
Ramón
R
Deulofeu
Department of Radiology, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain.
Luis San
LS
Román
Department of Radiology, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain; August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Laura
L
Oleaga
August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Ferran
F
Torres
August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Brain Ischemia and Neurodegeneration, Institute for Biomedical Research of Barcelona, Spanish Research Council, Barcelona, Spain.
Anna M
AM
Planas
D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011859:Radiography; D012044:Regression Analysis; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D014527:Uric Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D014527:Uric Acid