ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Poster Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Poster Presentations</h1> <P><b>Session Title:</b> Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS<br><b>Presentation Date:</b> Apr 15, 2010</P><h2 align='left'><B>RIFAXIMIN DECREASES VENOUS AMMONIA CONCENTRATIONS AND TIME-WEIGHTED AVERAGE AMMONIA CONCENTRATIONS CORRELATE WITH OVERT HEPATIC ENCEPHALOPATHY (HE) AS ASSESSED BY CONN SCORE IN A 6 MONTH STUDY</B></h2> <p align='left'><b>A. Sanyal</b><sup>1</sup>*, N. Bass<sup>2</sup>, F. Poordad<sup>3</sup>, M.Y. Sheikh<sup>4</sup>, K. Mullen<sup>5</sup>, S. Sigal<sup>6</sup>, T. Frederick<sup>7</sup>, R. Brown Jr.<sup>8</sup>, B. Bhandari<sup>9</sup>, S. Sedghi<sup>10</sup>, K. Merchant<sup>11</sup>, S. Huang<sup>11</sup>, A. Shaw<sup>11</sup>, E. Bortey<sup>11</sup>, W.P. Forbes<sup>11</sup><br> <em><sup>1</sup>Virginia Commonwealth University, Richmond, VA, <sup>2</sup>University of California, San Francisco, <sup>3</sup>Cedars-Sinai Medical Center, Los Angeles, <sup>4</sup>University of California at San Francisco, Fresno MEP, CA, <sup>5</sup>Case Western Reserve, Cleveland Clinic, Cleveland, OH, <sup>6</sup>Weill Medical College of Cornell University, New York, NY, <sup>7</sup>California Pacific Medical Center, San Francisco, CA, <sup>8</sup>Columbia University Medical Center, New York, NY, <sup>9</sup>Delta Research Partners, LLC, Monroe, LA, <sup>10</sup>Gastroenterology Associates of Central Georgia, LLC, Macon, GA, <sup>11</sup>Salix Pharmaceuticals, Inc., Morrisville, NC, USA. *asanyal@mcvh-vcu.edu</em></p><br> <p align='justify'><b><b>Background and aims: </b> </b>Elevated blood ammonia concentrations are quantitatively associated with central nervous system effects underlying HE, and may serve as a marker for HE severity. In a multinational trial (RFHE3001), rifaximin, a minimally absorbed, gut-selective antibiotic, reduced risk of breakthrough overt HE (primary endpoint) vs. placebo by 58% (hazard ratio, 0.421; p< 0.0001). The current analyses evaluated: <br> <ol> <li>the effect of rifaximin treatment on venous ammonia concentrations; </li> <li>the association between venous ammonia concentrations and breakthrough overt HE, as assessed by Conn score (CS). <br></li> </ol><b><b>Methods: </b></b> This double-blind, placebo-controlled trial evaluated rifaximin 550 mg BID for 6 months in patients with a history of HE. Eligible patients had cirrhosis, e"2 episodes of HE (CSe"2) within 6 months prior to screening, and were in remission (CS=0 or 1) at baseline. Continued therapy with lactulose was permitted in both arms. Breakthrough HE was an increase to CSe"2 or CS and asterixis grade increase of 1 each if baseline CS=0. Venous ammonia concentrations were measured at baseline and at Days 24, 84, and 168 during treatment. An area under the curve for ammonia concentration over time was normalized by exposure time (time-weighted average [TWA]). The correlation between TWA and the presence or absence of breakthrough HE episode was analyzed. A Receiver Operating Characteristic (ROC) curve analysis evaluated the accuracy of the correlation. <br><b><b>Results: </b></b> 299 patients were randomized to rifaximin (n=140) or placebo (n=159); 104 patients experienced HE breakthrough and 194 patients maintained remission. Rifaximin therapy decreased venous ammonia concentrations [mean change rifaximin (-5.7 µg/dL) versus placebo (-0.3 µg/dL): p=0.0391]. The difference between the frequency distributions of ammonia TWA in breakthrough HE (mean=102.4 µmol/L) versus remission (mean=85.4 µmol/L) subjects was statistically significant (p=0.0079), with a significant correlation between mean TWA and breakthrough HE (Spearman correlation coefficient=0.22, p=0.0005). The ROC curve value was 0.64 (95% CI 0.57-0.72). <br><b><b>Conclusions: </b></b> Rifaximin therapy protected against breakthrough overt HE and significantly decreased ammonia concentrations versus placebo. The TWA of venous ammonia concentrations independently predicted breakthrough HE in this 6 month study, underscoring the reliability and clinical relevance of CS-measured breakthrough HE episodes. <br></p> <br><a href='Session-P01-2b.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>