Levofloxacin versus moxifloxacin in nitazoxanide-based quadruple therapy as a first- and second-line treatment for Helicobacter pylori infection: NILE, a randomized, comparative, multicenter study

Abstract

<title>Abstract</title> <bold>Background:</bold> <italic>Helicobacter pylori</italic> infection remains a major global health concern, with rising antibiotic resistance posing significant challenges to eradication efforts. The search for novel, effective regimens is particularly important in regions with high resistance rates to standard agents. This study evaluated the efficacy and safety of nitazoxanide-based quadruple therapies incorporating either levofloxacin or moxifloxacin. <bold>Methods:</bold> In this randomized, multicenter trial, patients with confirmed <italic>H. pylori</italic>infection—both treatment-naïve and treatment-experienced—received either levofloxacin–nitazoxanide–doxycycline–lansoprazole (LNDL) or moxifloxacin–nitazoxanide–doxycycline–lansoprazole (MNDL) for 14 days. Naïve patients were also assigned to standard triple therapy with amoxicillin, clarithromycin, and lansoprazole (ACL). Eradication was assessed by stool antigen testing. Rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) methods, and adverse events were recorded. <bold>Results:</bold> Among naïve patients, ITT eradication rates were significantly higher with LNDL (82.3%) than with ACL (59.2%). PP analysis showed eradication rates of 87.2% for LNDL and 81.6% for MNDL, both significantly higher than ACL (60.9%). In treatment-experienced patients, ITT rates were 65.9% for LNDL and 77.3% for MNDL, with PP rates of 72.5% and 82.9%, respectively; differences between LNDL and MNDL were not statistically significant. All regimens were well tolerated, with no serious adverse events reported. <bold>Conclusion:</bold> Fluoroquinolone-containing nitazoxanide-based quadruple regimens showed acceptable efficacy and safety for H. pylori eradication in Egypt, where antibiotic resistance is high and bismuth availability is limited. Levofloxacin-based therapy achieved superior results in treatment-naïve patients, while both regimens were effective as rescue options. Although eradication rates did not reach the optimal threshold, these regimens represent practical alternatives when conventional regimens are not feasible. Further studies are warranted to optimize these strategies and address fluoroquinolone resistance. <bold>Trial registration</bold> This study has been registered as a randomized interventional trial in Clinical Trials Registry (ClinicalTrials.gov Identifier: NCT05184491) on the date of January 11, 2022.