Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China

Yong Xie, Zhenhua Zhu, Jiangbin Wang, Lingxia Zhang, Zhenyu Zhang, Hong Lu, Zhirong Zeng, Shiyao Chen, Dongsheng Liu, Nonghua Lv, the Chinese Study Group on Helicobacter pylori, Chinese Society of Gastroenterology, Yong Xie, Zhenhua Zhu, Jiangbin Wang, Lingxia Zhang, Zhenyu Zhang, Hong Lu, Zhirong Zeng, Shiyao Chen, Dongsheng Liu, Nonghua Lv, the Chinese Study Group on Helicobacter pylori, Chinese Society of Gastroenterology

Abstract

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method. The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively. There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance. The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported. Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance. (This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.).

Keywords: Helicobacter pylori; amoxicillin; antimicrobial safety; safety; tetracycline; treatment.

Copyright © 2018 Xie et al.

Figures

FIG 1
FIG 1
Flow diagram of this study. LR-BAC group, rabeprazole at 10 mg b.i.d. plus bismuth, amoxicillin, and clarithromycin; LR-BAT group, rabeprazole at 10 mg b.i.d plus bismuth, amoxicillin, and tetracycline; HR-BAC group, rabeprazole at 20 mg b.i.d. plus bismuth, amoxicillin, and clarithromycin; HR-BAT group, rabeprazole at 10 mg b.i.d plus bismuth, amoxicillin, and tetracycline. ITT, intention-to-treat; PP, per-protocol.

References

    1. Moayyedi P, Hunt RH. 2004. Helicobacter pylori public health implications. Helicobacter 9:67–72. doi:10.1111/j.1083-4389.2004.00250.x.
    1. Duck WM, Sobel J, Pruckler JM, Song Q, Swerdlow D, Friedman C, Sulka A, Swaminathan B, Taylor T, Hoekstra M, Griffin P, Smoot D, Peek R, Metz DC, Bloom PB, Goldschmidt S, Parsonnet J, Triadafilopoulos G, Perez-Perez GI, Vakil N, Ernst P, Czinn S, Dunne D, Gold BD. 2004. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg Infect Dis 10:1088–1094. doi:10.3201/eid1006.030744.
    1. Malfertheiner P, Chan FK, McColl KE. 2009. Peptic ulcer disease. Lancet 374:1449–1461. doi:10.1016/S0140-6736(09)60938-7.
    1. Moore JM, Salama NR. 2005. Mutational analysis of metronidazole resistance in Helicobacter pylori. Antimicrob Agents Chemother 49:1236–1237. doi:10.1128/AAC.49.3.1236-1237.2005.
    1. Hu Y, Zhu Y, Lu NH. 2017. Primary antibiotic resistance of Helicobacter pylori in China. Dig Dis Sci 62:1146–1154. doi:10.1007/s10620-017-4536-8.
    1. Liu WZ, Xie Y, Lu H, Cheng H, Zeng ZR, Zhou LY, Chen Y, Wang JB, Du YQ, Lu NH, on behalf of Chinese Society of Gastroenterology, Chinese Study Group on Helicobacter pylori and Peptic Ulcer. 2018. Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter 23:e12475. doi:10.1111/hel.12475.
    1. Graham DY, Fischbach L. 2010. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59:1143–1153. doi:10.1136/gut.2009.192757.
    1. Zheng Q, Chen WJ, Lu H, Sun QJ, Xiao SD. 2010. Comparison of efficacy of triple versus quadruple therapy on eradication of Helicobacter pylori and antibiotic resistance. J Dig Dis 11:313–318. doi:10.1111/j.1751-2980.2010.00457.x.
    1. Malfertheiner P, Bazzoli F, Delchier JC, Celiñski K, Giguère M, Rivière M, Mégraud F, Pylera Study Group. 2011. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomized, open-label, non-inferiority, phase 3 trial. Lancet 377:905–913. doi:10.1016/S0140-6736(11)60020-2.
    1. Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM, European Helicobacter and Microbiota Study Group and Consensus panel. 2017. Management of Helicobacter pylori infection—the MaastrichtV/Florence Consensus Report. Gut 66:6–30. doi:10.1136/gutjnl-2016-312288.
    1. Perri F, Festa V, Merla A, Quitadamo M, Clemente R, Andriulli A. 2002. Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection. Helicobacter 7:99–104. doi:10.1046/j.1083-4389.2002.00066.x.
    1. Liang X, Xu X, Zheng Q, Zhang W, Sun Q, Liu W, Xiao S, Lu H. 2013. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol 11:802–807. doi:10.1016/j.cgh.2013.01.008.
    1. Niv Y. 2005. Effectiveness of omeprazole-versus lansoprazole-based triple therapy for Helicobacter pylori eradication. Dig Dis Sci 50:839–841. doi:10.1007/s10620-005-2649-y.
    1. Miwa H, Nagahara A, Sato K, Ohkura R, Murai T, Shimizu H, Watanabe S, Sato N. 1999. Efficacy of 1 week omeprazole or lansoprazole-amoxycillin-clarithromycin therapy for Helicobacter pylori infection in the Japanese population. J Gastroenterol Hepatol 14:317–321. doi:10.1046/j.1440-1746.1999.01867.x.
    1. Sieg A, Sellinger M, Schlauch D, Hörner M, Fuchs W. 1999. Short-term triple therapy with lansoprazole 30 mg or 60 mg, amoxycillin and clarithromycin to eradicate Helicobacter pylori. Aliment Pharmacol Ther 13:865–868. doi:10.1046/j.1365-2036.1999.00540.x.
    1. Chiba N, Marshall CP. 2000. Omeprazole once or twice daily with clarithromycin and metronidazole for Helicobacter pylori. Can J Gastroenterol 14:27–31. doi:10.1155/2000/916417.
    1. Shimatani T, Moriwaki M, Xu J, Tazuma S, Inoue M. 2006. Acid-suppressive effects of rabeprazole: comparing 10 mg and 20 mg twice daily in Japanese Helicobacter pylori-negative and -positive CYP2C19 extensive metabolisers. Dig Liver Dis 38:802–808. doi:10.1016/j.dld.2006.06.002.
    1. Zhang W, Chen Q, Liang X, Liu W, Xiao S, Graham DY, Lu H. 2015. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy. Gut 64:1715–1720. doi:10.1136/gutjnl-2015-309900.
    1. Vallve M, Vergara M, Gisbert JP, Calvet X. 2002. Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis. Aliment Pharmacol Ther 16:1149–1156. doi:10.1046/j.1365-2036.2002.01270.x.
    1. Villoria A. 2008. Acid-related diseases: are higher doses of proton pump inhibitors more effective in the treatment of Helicobacter pylori infection? Gastroenterol Hepatol 31:546–547. doi:10.1157/13127103.
    1. Xie Y, Zhu Y, Zhou H, Lu ZF, Yang Z, Shu X, Guo XB, Fan HZ, Tang JH, Zeng XP, Wen JB, Li XQ, He XX, Ma JH, Liu DS, Huang CB, Xu NJ, Wang NR, Lu NH. 2014. Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection. World J Gastroenterol 20:11415–11421. doi:10.3748/wjg.v20.i32.11415.
    1. Kuwayama H, Asaka M, Sugiyama T, Fukuda Y, Aoyama N, Hirai Y, Fujioka T, Japan Rabeprazole Study Group. 2007. Rabeprazole-based eradication therapy for Helicobacter pylori: a large-scale study in Japan. Aliment Pharmacol Ther 25:1105–1113. doi:10.1111/j.1365-2036.2007.03298.x.
    1. Hsu PI, Lai KH, Wu CJ, Tseng HH, Tsay FW, Peng NJ, Chen TA, Chuah SK, Lin WS, Lo GH. 2007. High-dose versus low-dose esomeprazole-based triple therapy for Helicobacter pylori infection. Eur J Clin Invest 37:724–730. doi:10.1111/j.1365-2362.2007.01852.x.
    1. Hsu PI, Wu DC, Chen A, Peng NJ, Tseng HH, Tsay FW, Lo GH, Lu CY, Yu FJ, Lai KH. 2008. Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures. Eur J Clin Invest 38:404–409. doi:10.1111/j.1365-2362.2008.01951.x.
    1. bioMerieux SA. 2012. Etest application guide. bioMerieux SA, Marcy-l'Etoile, France: .

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅