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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\u003EResults from the PROTECT (A Placebo-controlled Randomized study of the selective A1 adenosine receptor antagonist KW-3902 for patients hospitalized with acute heart failure and volume Overload to assess Treatment Effect on Congestion and renal function Trial) trial failed to meet both the primary and secondary endpoints of the study.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERenal Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from the PROTECT (A Placebo-controlled Randomized study of the selective A\u003Csub\u003E1\u003C\/sub\u003E adenosine receptor antagonist KW-3902 for patients hospitalized with acute heart failure and volume Overload to assess Treatment Effect on Congestion and renal function Trial) trial, presented at the European Society of Cardiology\u0027s annual meeting in Barcelona, Spain, by Professor Marco Metra, MD, University of Brescia, Brescia, Italy, failed to meet both the primary and secondary endpoints of the study.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe objectives of PROTECT were to assess the efficacy and safety of the adenosine A\u003Csub\u003E1\u003C\/sub\u003E receptor antagonist rolofylline versus placebo on symptoms, renal function, and short-term morbidity and mortality in 2033 patients who were hospitalized with heart failure (HF) within 24 hours with signs of fluid overload, impaired renal function (estimated GFR 20\u201380 ml\/min), and high serum levels of B-type natriuretic peptide (BNP \u0026gt;500 pg\/mL) or N-terminal fragment of B-type natriuretic peptide (NT-proBNP \u0026gt;2000 pg\/mL). Rolofylline 30 mg\/day or placebo (2:1 ratio) was administered in a double-blind fashion as a 4-hour daily infusion that was repeated for 3 days. Subjects were predominantly male (67%) who had a mean age of 70 years, mean creatinine clearance \u223c50 mL\/min, and mean serum creatinine (SCr) 1.5 mg\/dL. Most subjects were receiving multiple HF medications within the 2 weeks prior to study enrollment, including ACE inhibitor or ARB (75%), beta-blocker (76%), aldosterone inhibitor (43%), and digoxin (28%).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe primary study outcome was a three-category ordered outcome: treatment success (moderate to marked improvement of dyspnea at 24 and 48 hours with no evidence of treatment failure); subject unchanged; or treatment failure (death or readmission for HF through Day 7, or worsening signs\/symptoms of HF occurring \u0026gt;24 hours after the start of the study through Day 7 or discharge, or persistent renal impairment [SCr increase \u22650.3 mg\/dL at Days 7 and 14, or the initiation of hemofiltration or dialysis through Day 7]). Secondary outcomes included time to death or rehospitalization for renal or cardiovascular causes through Day 60 and the proportion of subjects with renal impairment, as defined in the primary endpoint.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThere was no significant difference in the primary endpoint, wherein 40.6% of rolofylline subjects versus 36% of placebo subjects achieved treatment success, 37.5% versus 44.2% remained unchanged, and 21.8% versus 19.8% were classified as treatment failures (OR, 0.92; 95% CI, 0.78 to 1.09; p=0.35), nor was a difference observed in the secondary endpoint of persistent renal impairment (15.0% vs 13.7%, OR, 1.11; 95% CI, 0.85 to 1.46; p=0.44). Furthermore, rolofylline appeared to increase neurological complications, including seizures (11 subjects [0.8%] vs no subjects on placebo), stroke (16 [1.2%] vs 3 [0.5%]), and serious adverse events that involved the nervous system (1.5% vs 0.6%).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAlthough the smaller PROTECT Pilot trial had shown promise for rolofylline in preventing dyspnea and renal failure, due to the lack of efficacy and apparent increase in nervous system disorders in this larger trial, further study of rolofylline in HF has been halted. Additional studies with alternative selective adenosine A\u003Csub\u003E1\u003C\/sub\u003E-receptor antagonists are ongoing.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2009 MD Conference Express\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\/9\/4\/12.1.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?nzmisp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}