Document Detail

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.
MedLine Citation:
PMID:  19920806     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: 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. METHODS: 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. RESULTS: 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 treatment in a dose-dependent manner (121+/-11 mm Hg after NCX-1000 vs. 136+/-7 mm Hg at baseline; P=0.003). Seven non-serious adverse events were experienced by four patients (one on placebo). CONCLUSIONS: In patients with cirrhosis and portal hypertension, NCX-1000 administration was safe, but it was not able to reduce portal pressure. A significant reduction of systolic blood pressure and HBF was observed in the treatment arm, suggesting that the drug had systemic effects and lacked selective release of NO at the intrahepatic circulation.
Annalisa Berzigotti; Pau Bellot; Andrea De Gottardi; Juan Carlos Garcia-Pagan; Caroline Gagnon; Jean Sp?nard; Jaime Bosch
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Publication Detail:
Type:  Clinical Trial, Phase II; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-11-17
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  105     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1094-101     Citation Subset:  IM    
Hepatic Hemodynamics Laboratory, Hospital Cl?nic-IDIBAPS, University of Barcelona, Barcelona, Spain.
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MeSH Terms
Administration, Oral
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Follow-Up Studies
Hypertension, Portal / diagnosis,  drug therapy*,  etiology
Liver Circulation / drug effects
Liver Cirrhosis / complications,  diagnosis,  drug therapy*
Maximum Tolerated Dose
Middle Aged
Nitrates / administration & dosage*,  adverse effects
Nitric Oxide Donors / administration & dosage*,  adverse effects
Portal Pressure / drug effects*
Reference Values
Risk Assessment
Severity of Illness Index
Treatment Failure
Ursodeoxycholic Acid / administration & dosage,  adverse effects,  analogs & derivatives*
Reg. No./Substance:
0/2-methyl-3-(2-((4-nitrooxybutyloxy)carbonyl)vinyl)phenyl ursodeoxycholic acid ester; 0/Nitrates; 0/Nitric Oxide Donors; 128-13-2/Ursodeoxycholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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