NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study

The American Journal of Gastroenterology
Annalisa BerzigottiJaime Bosch

Abstract

NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension. This was a single-center, phase-2a, randomized (4:1), double-blind, parallel-group, dose-escalating study. Patients received progressive oral doses of NCX-1000 or placebo up to 2 g t.i.d. or maximum tolerated doses for 16 days. Efficacy on fasting and postprandial hepatic venous pressure gradient (HVPG) at baseline and after treatment was assessed. Hepatic blood flow (HBF) and arterial blood pressure were also measured. Eleven patients (nine NCX-1000 and two placebo) were enrolled and completed the trial. After NCX-1000 treatment, HVPG did not change (16.7+/-3.8 vs. 17.1+/-3.8 mm Hg; P=0.596), and HBF decreased significantly (904+/-310 vs. 1,129+/-506 ml/min; P=0.043). The postprandial increase in portal pressure and HBF was not modified by NCX-1000. There was no significant effect on diastolic blood pressure, but systolic blood pressure was reduced by the t...Continue Reading

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Citations

Nov 23, 2011·Critical Care : the Official Journal of the Critical Care Forum·Len VerbekeWim Laleman
Apr 5, 2013·World Journal of Gastroenterology : WJG·Liang Shuo HuJian Hua Wang
May 24, 2017·Gastroenterology Report·Philipp Schwabl, Wim Laleman
Sep 18, 2010·The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi·Jin Woo Lee
Jul 13, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Yasuko Iwakiri
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Jun 22, 2010·Journal of Hepatology·Jaume BoschJuan Carlos García-Pagán

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