Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN

"La capacidad neuroprotectora de la administración exógena de AU se ha demostrado en modelos de isquemia experimental in vitro e in vivo, así como en modelos de daño inflamatorio del sistema nervioso central (encefalitis alérgica experimental). Su efecto neuroprotector se ha asociado tanto a su acción antioxidante como a la reducción de la excitotoxicidad por glutamato o a la protección de la barrera hematoencefálica6,7. En el modelo intraluminal de isquemia cerebral permanente o transitoria de rata, la administración exógena de AU reduce el volumen de la lesión y el grado de afectación neurológica5.", El estracto es del artículo Ácido úrico: un neuroprotector en busca de patrocinador publicado en el numero 1 de la Revista de nuestro grupo en Junio de 2007. Pues bien ya se ha encontrado partrocinador y no es ni más ni menos que el Instituto de Salud Carlos III. El proyecto de estrudio ha sido publicado en la revista Int J Stroke. 2010 Aug;5(4):325-8 y se puede consultar en ClinicalTrials.gov

The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms.

Amaro S, Cánovas D, Castellanos M, Gállego J, Martí-Fèbregas J, Segura T, Chamorro A.

Comprehensive Stroke Center, Institute of Neurosciences, Hospital Clínic, Institute Investigacions Biomèdicas August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Abstract

Rationale Oxidative stress is a major contributor to brain damage in patients with ischaemic stroke. Uric acid (UA) is a potent endogenous antioxidant molecule. In experimental ischaemia in rats, the exogenous administration of uric acid is neuroprotective and enhances the effect of rtPA. Moreover, in acute stroke patients receiving rtPA within 3 h of stroke onset, the intravenous administration of uric acid is safe, prevents an early decline in uric acid levels and reduces an early increase in oxidative stress markers and in active matrix metalloproteinase nine levels. Aim To determine whether the combined treatment with uric acid and rtPA is superior to rtPA alone in terms of clinical efficacy in acute ischaemic stroke patients treated within the first 4.5 h of onset of symptoms. Study design Multicentre, interventional, randomised, double-blind and vehicle-controlled efficacy study with parallel assignment (1 : 1). Estimated enrolment: 420 patients over 3 years, starting in January 2010. Treatment arms included patients will receive a single intravenous infusion of 1 g of UA dissolved in a vehicle (500 ml of 0.1% lithium carbonate and 5% mannitol) (n=210) or vehicle alone (n=210). Inclusion and exclusion criteria: the study will include patients older than 18 years, treated with rtPA within the first 4.5 h of clinical onset and with a baseline National Institute of Health Stroke Scale score >6 and <25 and a modified Rankin Scale score </=2 before the ischaemic event. Patients with renal insufficiency, gout or asymptomatic hiperuricaemia treated with allopurinol will be excluded. Study outcomes The primary outcome measure is the proportion of patients achieving an modified Rankin Scale of 0 to 1 at 3 months after treatment or two in those patients with a prior qualifying modified Rankin Scale of 2. Secondary outcome measures include the final infarction volume measured at 72 h and the proportion of patients with symptomatic intracranial haemorrhage (>/=4 points of increase in the National Institute of Health Stroke Scale score).