{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzpd43\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzpd43\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/1\\\/10\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/1\\\/10\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/1\\\/10\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/1\\\/10\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article presents results from the Efficacy Study of Combined Treatment With Uric Acid and rt-PA in Acute Ischemic Stroke [URICO-ICTUS; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00860366\u0026amp;atom=%2Fspmdc%2F14%2F1%2F10.atom\u0022\u003ENCT00860366\u003C\/a\u003E], a Phase 3 investigator-driven, multicenter, randomized, placebo-controlled efficacy study to determine whether combined treatment with uric acid and recombinant tissue plasminogen activator (rt-PA) is clinically superior to rt-PA alone.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003E\u00c1ngel Chamorro, MD, PhD, University of Barcelona, Barcelona, Spain, presented results from the Efficacy Study of Combined Treatment With Uric Acid and rt-PA in Acute Ischemic Stroke [URICO-ICTUS; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00860366\u0026amp;atom=%2Fspmdc%2F14%2F1%2F10.atom\u0022\u003ENCT00860366\u003C\/a\u003E], a Phase 3 investigator-driven, multicenter, randomized, placebo-controlled efficacy study to determine whether combined treatment with uric acid and recombinant tissue plasminogen activator (rt-PA) is clinically superior to rt-PA alone.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAlthough this study failed to reach its prespecified outcome of a 14% absolute improvement in excellent outcome, the results suggest that adding uric acid to rt-PA therapy is safe, may prevent early stroke worsening, may improve overall mRS score, and might facilitate full independence in patients with acute stroke.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EUric acid has been shown to have antioxidant properties in both animal and human studies. In the rat, uric acid administered early after a stroke reduces infarct volume, protects both cortical and subcortical brain areas, attenuates the inflammatory response, and extends the benefits of rt-PA [Romanos E et al. \u003Cem\u003EJ Cereb Blood Flow Metab\u003C\/em\u003E 2007]. Results of a Phase 2 study in patients with acute stroke treated with rt-PA showed that intravenous administration of uric acid in patients was safe, prevented an early decline in uric acid levels, and reduced the early increase in oxidative stress markers [Amaro S et al. \u003Cem\u003EStroke\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EParticipants were adult patients (n=421) treated with 0.9 mg\/kg of rt-PA (alteplase) within the first 4.5 hours of stroke symptoms, a baseline NIHSS score \u0026gt;6 and \u0026lt;25, and a premorbid mRS score \u22642 before the ischemic event. Within 1 hour of their rt-PA infusion, patients were randomized to either uric acid (1 g; n=215), or placebo (n=206). NIHSS was assessed at 0, 2, 24, 48, and 72 hours, and again at Days 5 and 90. The Barthel Index and mRS were performed at Day 90. The primary study outcome was having an mRS score of 0 to 1 (2 for patients with a premorbid score of 2) at 90 days. Secondary outcomes included the proportion of patients with NIHSS \u22641 at 2 hours, ischemic worsening at 72 hours, and ordinal mRS, NIHSS, and the proportion of patients achieving a Barthel score of 95 to 100 at Day 90. Safety outcomes included incidence of symptomatic intracranial hemorrhage at 36 hours, the total incidence of gout, and death at Day 90.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ESubjects were median age of 76 years (range, 66 to 82), \u223c50% men, and had comorbidities typical for this population of patients. The media NIHSS score was 13, median time to rt-PA was \u223c2.5 hours, and the median time to initiation of uric acid therapy was \u223c3 hours.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EFull analysis data set was comprised of 411 patients (uric acid, n=211; placebo, n=200). The proportion of patients having an excellent outcome (ie, mRS 0\u20131 or 0\u20132 if premorbid mRS was 2) was 39.3% in the uric acid group and 33% in the placebo group (RR, 1.23; 95% CI, 0.96 to 1.56; p=0.099). Secondary outcomes favored the patients in the uric acid group but were not significantly different. The ordinal OR for mRS was 1.40 (95% CI, 0.99 to 1.98; p=0.057). The median mRS was 2 in the uric acid group and 3 in the placebo group (p=0.045). The percentage of patients with NIHSS score \u0026lt;1 at 2 hours or Day 90 was similar. Significantly more patients in the placebo group experienced ischemic worsening by Day 3 compared with uric acid (9.0% vs 3.3%; RR, 0.34; 95% CI, 0.14 to 0.85; p=0.021). The proportion of patients with a Barthel score \u0026gt;94 at 90 days was 48.3% in the uric acid group and 40.5% in the placebo group (p=0.057). There were no safety concerns, differences in the rate of bleeding, incidence of gout, or deaths between the groups.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EExploratory analysis showed that women (who naturally have lower levels of uric acid), patients with low baseline NIHSS values (\u226410), and those with lower glucose levels had better outcomes with combination uric acid plus rt-PA treatment.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/1\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzpd43\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}