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Table 1 Inclusion and exclusion criteria a

From: 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

Inclusion criteria Exclusion criteria
Age ≥18 years. Age <18 years.
Written informed consent to participate in the clinical trial and written informed consent for genetic testing. Absent written informed consent to participate in the clinical trial or for genetic testing.
Patients have to be able to understand and follow instructions and to be willing to attend all study visits (compliance). Patients unable to understand the meaning of the clinical trial and the consequences of study participation.
Presence or history of ascites in case of advanced liver disease compatible with cirrhosis (liver biopsy not required). Patients unable to understand or follow instructions or not willing to attend all study visits.
Diagnostic paracentesis to exclude SBP within 10 days before the baseline visit. Patients who cannot undergo paracentesis because of small amounts of ascites can only be included in the trial if SBP is unlikely, taking into account clinical and blood test indicators. Simultaneous participation in another clinical trial (study medication has to be stopped for almost 30 days before the baseline visit).
Positive genotyping result for at least one of the NOD2 risk variants p.R702W, p.G908R or c.3020insC. Persistent drug abuse (alcohol abuse may be tolerated in the setting of adequate compliance).
Pregnancy is to be excluded by a pregnancy test (beta-hCG blood test or urine test) in women with childbearing potential who have not undergone surgical contraceptive methods or hysterectomy. These patients have to use effective contraceptive methods. Pregnancy, planned pregnancy or breastfeeding patients.
  Patients without a history of ascites.
  SBP diagnosed by the index paracentesis within 10 days before baseline.
  Previous history of SBP. (When this is uncertain, absence of a secondary antibiotic prophylaxis may be used as an alternative criterion to exclude SBP.)
  Long-term antibiotic prophylaxis, irrespective of the indication. Long-term treatment is to be completed at least 28 days before randomization.
  Contraindications against norfloxacin or placebo such as the following:
  • Intolerance to norfloxacin, to substances with related chemical structure or to other components of norfloxacin or placebo.
  • Patients with acquired long QT syndrome or other nonmodifiable risk factors causing a persisting corrected QT prolongation (corrected according to Bazett’s formula: >470 ms for men and >480 ms for women).
  • Patients with galactose intolerance, lactamase deficiency or glucose and/or galactose malabsorption.
  • Patients with myasthenia gravis.
  • Patients with tendinitis or tendon rupture linked to fluoroquinolone intake.
  Patients with a life expectancy of less than 12 months due to hepatocellular cancer, other malignant diseases or another severe comorbidity.
  Patients with HIV infection with a CDC classification clinical stage C or laboratory stage 3.
  1. aCDC, Centers for Disease Control and Prevention; hGC, Human chorionic gonadotropin; NOD2, nucleotide-binding oligomerization domain containing 2; SBP, Spontaneous bacterial peritonitis.