You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Uric Acid Levels Are Relevant in Patients With Stroke Treated With Thrombolysis
Abstract 1:
Background and Purpose — Uric acid ( UA ) is a neuroprotective antioxidant that improves the benefits of alteplase in experimental ischemia . However , it is unknown whether endogenous UA also influences the response to thrombolysis in patients with stroke . Methods — A total of 317 consecutive patients treated with thrombolysis  were included in a prospect i ve stroke registry . Demographics , laboratory data , neurological course , and infa rct ion volume were prospect ively collected . Excellent outcome was defined as achieving a modified Rankin Scale score < 2 at 90 days . Binary and ordinal logistic regression models were used to analyze modified Rankin Scale score at 90 days . Results — UA levels were significantly higher in patients with an excellent outcome than in patients with a poor outcome ( 5.82 [ 1.39 ] versus 5.42 [ 1.81 ] , P=0.029 ) . In multivariate models , increased UA levels ( OR , 1.23 ; 95 % CI , 1.03 to 1.49 ; P=0.025 ) were associated with an excellent outcome and with an increased risk of shifting to a better category across the modified Rankin Scale ( OR , 1.19 ; 95 % CI , 1.04 to 1.38 ; P=0.014 ) independently of the effect of confounders . The levels of UA and the volume of final infa rct ion were inversely correlated ( r=−0.216 , P<0.001 ) and the inverse correlation remained after adjustment for age , sex , and baseline National Institutes of Health Stroke Scale score ( t value=−2.54 , P=0.01 ) . Significantly lower UA levels were found in patients with malignant middle cerebral artery infa rct ion and parenchymal hemorrhage postthrombolysis . Conclusions — Increased UA serum levels are associated with better outcome in patients with stroke treated with reperfusion therapies . These results support the assessment of the potential neuroprotective role of the exogenous administration of UA in patients with stroke treated with thrombolysis


Title 2:
Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial
Abstract 2:
INTRODUCTION 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 r and omised , 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 r and omly 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 r and omly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication ) . The study is registered with Clinical Trials.gov , number NCT00860366 . FINDINGS Between July 1 , 2011 , and April 30 , 2013 , we r and omly 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 clinical ly 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 ) . INTERPRETATION 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 . FUNDING Institute of Health Carlos III of the Spanish Ministry of Health and Fundación Doctor Melchor Colet


Title 3:
Antioxidant Profile and Early Outcome in Stroke Patients
Abstract 3:
Background and Purpose Experimental studies provide evidence of an association between ischemic stroke and increased oxidative stress , but data in humans are still limited and controversial . The purpose of this study was to investigate the time course of plasma antioxidant changes in ischemic stroke patients . Methods Plasma antioxidants , including water-soluble ( vitamin C and uric acid ) and lipid-soluble ( vitamins A and E ) compounds as well as antioxidant enzyme activities in plasma ( superoxide dismutase [ SOD ] and glutathione peroxidase ) and erythrocytes ( SOD ) , were measured by high-performance liquid chromatography ( antioxidant vitamins ) and by spectrophotometry ( antioxidant enzymes ) in 38 subjects ( 25 men and 13 women aged 77.2±7.9 years ) with acute ischemic stroke of recent onset ( < 24 hours ) on admission , after 6 and 24 hours , and on days 3 , 5 , and 7 . Antioxidant levels in patients on admission were compared with those of age- and sex-matched controls . Results Mean antioxidant levels and activities in patients on admission were lower than those of controls and showed a gradual increase over time . Patients with the worst early outcome ( death or functional decline ) had higher vitamin A and uric acid plasma levels and lower vitamin C levels and erythrocyte SOD activity than those who remained functionally stable . Conclusions These results suggest that the majority of antioxidants are reduced immediately after an acute ischemic stroke , possibly as a consequence of increased oxidative stress . A specific antioxidant profile is associated with a poor early outcome


Title 4:
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
Abstract 4:
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 , r and omised , 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 infa rct ion 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 )


Title 5:
Urate predicts subsequent cardiac death in stroke survivors.
Abstract 5:
AIMS To test the hypothesis that urate predicts cardiac death after stroke independent of conventional risk factors of atherosclerosis , creatinine and diuretic use . METHODS AND RESULTS Serum urate concentration was measured in an unselected cohort of 354 stroke survivors who were followed-up for a median of 2.8 years .  Cardiac death was the primary end-point . Urate was associated with a statistically significant threefold increase in relative risk of cardiac death even after adjustment for other conventional risk factors . In the subgroup of patients who were not on diuretics , raised urate was associated with a 12-fold significant increase in relative risk of cardiac death after adjusting for renal function and other conventional risk factors . A urate concentration of greater than 0.31 mmol . l(-1 ) was 78 % sensitive at predicting cardiac death within 5 years after stroke , but was only 54 % specific . If urate exceeded 0.38 mmol . l(-1 ) , specificity of predicting cardiac death within 5 years after stroke was 88 % . CONCLUSIONS Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke . This appeared to be true even in stroke survivors who were not on diuretic therapy


Title 6:
Is uric acid protective or deleterious in acute ischemic stroke? A prospective cohort study.
Abstract 6:
Contrasting observations have been made between serum urate and ischemic stroke outcomes in studies involving Caucasian population s. To assess the hypothesis that urate is associated with stroke outcomes , a prospect i ve follow-up study was performed in a cohort of Asian patients with ischemic stroke . Patients diagnosed with transient ischemic attack , first or recurrent ischemic stroke were included in this study . Serum urate , measured using high-performance liquid chromatography , was correlated with 12-month functional and vascular stroke outcomes . Poor functional outcome was defined as a modified Rankin scale exceeding 2 and vascular outcome was defined as a composite of recurrent stroke , myocardial infa rct ion or vascular death during the study period . A total of 503 patients of mean age 63 ( SD 12 ) years were included . A U-shaped relationship between urate quartiles and poor functional outcomes was demonstrated . More patients with low ( < 280microM ) and high ( > 410microM ) urate levels had poor functional outcomes ( 36 % and 27 % respectively ) , compared to those with urate levels between 340 and 410microM ( 14 % ) . No significant relationship was observed between urate and vascular outcomes . Depending on its level , serum urate may exhibit protective and deleterious effects on stroke outcomes
This meta- analysis supports that serum uric acid level has a protective effect on neurological outcome after acute ischemic stroke .
High uric acid level at the onset is a biomarker of better prognosis in patients with acute ischemic stroke