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Effects of Long-term Norfloxacin Therapy in Patients with Advanced Cirrhosis.
Gastroenterology. 2018 Aug 22;:
Authors: Moreau R, Elkrief L, Bureau C, Perarnau JM, Thévenot T, Saliba F, Louvet A, Nahon P, Lannes A, Anty R, Hillaire S, Pasquet B, Ozenne V, Rudler M, Ollivier-Hourmand I, Robic MA, d'Alteroche L, Di Martino V, Ripault MP, Pauwels A, Grangé JD, Carbonell N, Bronowicki JP, Payancé A, Rautou PE, Valla D, Gault N, Lebrec D, NORFLOCIR Trial Investigators
Abstract
BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.
METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy; the study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n=144) or placebo (n=147), once-daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow up.
RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P=.21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (sub-distribution hazard ratio [SHR], 0.59; 95% CI, 0.35-0.99). The SHR for death at 6 months with norfloxacin vs placebo was 0.35 (95% CI, 0.13-0.93) in patients with ascites fluid protein concentrations of less than 15 g/L and 1.39 (95% CI, 0.42-4.57) in patients with ascites fluid protein concentrations of 15 g/L or more. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria.
CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov no: NCT01037959.
PMID: 30144431 [PubMed - as supplied by publisher]