The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) : study protocol for a randomized controlled trial

  • Background: Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. Methods/Design: The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (<15 versus ≥15 g/L) and the study site is planned. In this multicenter national study, patients are recruited in at least 13 centers throughout Germany. The key inclusion criterion is the presence of a NOD2 risk variant in patients with decompensated liver cirrhosis. The most important exclusion criteria are current SBP or previous history of SBP and any long-term antibiotic prophylaxis. The primary endpoint is overall survival after 12 months of treatment. Secondary objectives are to evaluate whether the frequencies of SBP and other clinically relevant infections necessitating antibiotic treatment, as well as the total duration of unplanned hospitalization due to cirrhosis, differ in both study arms. Recruitment started in February 2014. Discussion: Preventive strategies are required to avoid life-threatening infections in patients with liver cirrhosis, but unselected use of antibiotics can trigger resistant bacteria and worsen outcome. Thus, individualized approaches that direct intervention only to patients with the highest risk are urgently needed. This trial meets this need by suggesting stratified prevention based on genetic risk assessment. To our knowledge, the INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. Trial registrations: German Clinical Trials Register DRKS00005616. Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26. Registered 26 January 2015.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Markus Casper, Martin Mengel, Christine Fuhrmann, Eva HerrmannORCiDGND, Beate Appenrodt, Peter Schiedermaier, Matthias Reichert, Tony BrunsORCiDGND, Cornelius EngelmannORCiDGND, Frank Grünhage, Frank Lammert
URN:urn:nbn:de:hebis:30:3-372404
DOI:https://doi.org/10.1186/s13063-015-0594-4
ISSN:1468-6694
ISSN:1745-6215
ISSN:1468-6708
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25887140
Parent Title (English):Trials
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2015/03/08
Date of first Publication:2015/03/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:INCA trial group
Release Date:2015/04/25
Tag:Genetic testing; Liver cirrhosis; Portal hypertension; Primary prophylaxis; Spontaneous bacterial peritonitis
Volume:16
Issue:83
Page Number:8
Note:
Copyright © Casper et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS-PPN:369050088
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0