Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area

Sotirios Georgopoulos (1) , Elias Xirouchakis (1) , Beatrice Martinez-Gonzales (2) , Evanthia Zampeli (3) , Elias Grivas (4) , Charikleia Spiliadi , Maria Sotiropoulou (3) , Kalliopi Petraki (5) , Kostantinos Zografos (1) , Fotini Laoudi (1) , Dionysios Sgouras (2) , Andreas Mentis (2) , Panagiotis Kasapidis (4) , Spyros Michopoulos (3)

1 Paleo Faliro Clinic [Athens]
2 Laboratoire de microbiologie médicale = Laboratory of Medical Microbiology [Athènes]
3 Alexandra hospital [Athens, Greece]
4 Central Clinic of Athens
5 Metropolitan Hospital [Athens]

BACKGROUND: Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations. MATERIALS AND METHODS: This multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by (13)C-urea breath test or histology 4-6weeks after treatment. Adverse events and adherence were evaluated. RESULTS: Allocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7-18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6-17.6). Overall, adherence was (98.9%, 95% CI=97-100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5-33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment. CONCLUSIONS: Concomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.

Mots clés: Clarithromycin resistance; Concomitant treatment; First line; H. pylori treatment; Metronidazole resistance; Sequential treatment

Domaines: Bactériologie; Anatomie, Histologie, Anatomopathologie [q-bio.TO]; Hépatologie et Gastroentérologie

Sotirios Georgopoulos, Elias Xirouchakis, Beatrice Martinez-Gonzales, Evanthia Zampeli, Elias Grivas, et al.. Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area. European Journal of Internal Medicine, 2016, 32, pp.84-90. ⟨10.1016/j.ejim.2016.04.011⟩. ⟨pasteur-02195951⟩