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Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days

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Abstract

Background

Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori.

Methods

Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication.

Results

The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups.

Conclusion

Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

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Data availability

No datasets were generated or analysed during the current study.

References

  1. Ren S, Cai P, Liu Y et al. Prevalence of Helicobacter pylori infection in China: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2022;37:464–470. https://doi.org/10.1111/jgh.15751.

    Article  PubMed  Google Scholar 

  2. Xia C, Dong X, Li H et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022;135:584–590. https://doi.org/10.1097/cm9.0000000000002108.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liu WZ, Xie Y, Lu H et al. Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter. 2018;23:e12475. https://doi.org/10.1111/hel.12475.

    Article  PubMed  Google Scholar 

  4. Malfertheiner P, Megraud F, O’Morain CA et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30. https://doi.org/10.1136/gutjnl-2016-312288.

    Article  CAS  PubMed  Google Scholar 

  5. Liou JM, Malfertheiner P, Lee YC et al. Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus. Gut. 2020;69:2093–2112. https://doi.org/10.1136/gutjnl-2020-322368.

    Article  PubMed  Google Scholar 

  6. Zhou L, Lu H, Song Z et al. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl). 2022;135:2899–2910. https://doi.org/10.1097/CM9.0000000000002546.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kato MA-O, Ota H, Okuda MA-O, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 Revised Edition. Helicobacter. 2019.

  8. Jung HK, Kang SJ, Lee YC et al. Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020. Gut Liver. 2021;15:168–195. https://doi.org/10.5009/gnl20288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ding YM, Li YY, Liu J et al. The cure rate of 10-day bismuth-containing quadruple therapy for Helicobacter pylori eradication is equivalent to 14-day: a systematic review and meta-analysis. Clin Exp Med. 2022. https://doi.org/10.1007/s10238-022-00953-7.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Qiao C, Li Y, Liu J et al. Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area. J Gastroenterol Hepatol. 2021;36:2383–2388. https://doi.org/10.1111/jgh.15468.

    Article  CAS  PubMed  Google Scholar 

  11. D’Agostino RB Sr, Massaro JM, Sullivan LM. Non-inferiority trials: design concepts and issues - the encounters of academic consultants in statistics. Stat Med. 2003;22:169–186. https://doi.org/10.1002/sim.1425.

    Article  PubMed  Google Scholar 

  12. Liu DS, Wang YH, Zeng ZR et al. Primary antibiotic resistance of Helicobacter pylori in Chinese patients: a multiregion prospective 7-year study. Clin Microbiol Infect. 2018;24:e5–e8. https://doi.org/10.1016/j.cmi.2017.11.010.

    Article  CAS  Google Scholar 

  13. Han Z, Li Y, Kong Q et al. Efficacy of bismuth for antibiotic-resistant Helicobacter pylori strains eradication: A systematic review and meta-analysis. Helicobacter. 2022;27:e12930. https://doi.org/10.1111/hel.12930.

    Article  CAS  PubMed  Google Scholar 

  14. Qian HS, Li WJ, Dang YN, et al. Ten-Day Vonoprazan-Amoxicillin Dual Therapy as a First-Line Treatment of Helicobacter pylori Infection Compared With Bismuth-Containing Quadruple Therapy. Am J Gastroenterol. 2023;118:627–34. https://doi.org/10.14309/ajg.0000000000002086.

  15. Graham DY. It Is Time for a Paradigm Shift in Design, Execution, and Publishing of Comparative Helicobacter pylori Treatment Trials. Am J Gastroenterol. 2023;118:1154–6. https://doi.org/10.14309/ajg.0000000000002298.

  16. Xu H, Yun J, Li R et al. Antibiotics Resistance Prevalence of Helicobacter pylori Strains in Northwest China. Infect Drug Resist. 2022;15:5519–5528. https://doi.org/10.2147/IDR.S383444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shu X, Ye D, Hu C et al. Alarming antibiotics resistance of Helicobacter pylori from children in Southeast China over 6 years. Sci Rep. 2022;12:17754. https://doi.org/10.1038/s41598-022-21661-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kong Q, Li Y, Li R et al. Low compliance to post-screening recommendations in a family-based Helicobacter pylori screening and treatment program: A prospective cohort study. Helicobacter. 2022;27:e12912. https://doi.org/10.1111/hel.12912.

    Article  CAS  PubMed  Google Scholar 

  19. Tsuda M, Asaka M, Kato M, et al. Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan. Helicobacter. 2017;22. https://doi.org/10.1111/hel.12415.

  20. Deguchi H, Uda A, Murakami K. Current Status of Helicobacter pylori Diagnosis and Eradication Therapy in Japan Using a Nationwide Database. Digestion. 2020;101:441–449. https://doi.org/10.1159/000500819.

    Article  CAS  PubMed  Google Scholar 

  21. Gao K, Wu J. National trend of gastric cancer mortality in China (2003–2015): a population-based study. Cancer Commun (Lond). 2019;39:24. https://doi.org/10.1186/s40880-019-0372-x.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Han Y, Yan T, Ma H et al. Cost-Effectiveness Analysis of Helicobacter pylori Eradication Therapy for Prevention of Gastric Cancer: A Markov Model. Dig Dis Sci. 2020;65:1679–1688. https://doi.org/10.1007/s10620-019-05910-1.

    Article  CAS  PubMed  Google Scholar 

  23. Mason J, Axon AT, Forman D et al. The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial. Aliment Pharmacol Ther. 2002;16:559–568. https://doi.org/10.1046/j.1365-2036.2002.01204.x.

    Article  CAS  PubMed  Google Scholar 

  24. Chiang TH, Chang WJ, Chen SL et al. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut. 2021;70:243–250. https://doi.org/10.1136/gutjnl-2020-322200.

    Article  CAS  PubMed  Google Scholar 

  25. Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008;5:321–331. https://doi.org/10.1038/ncpgasthep1138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hori Y, Imanishi A, Matsukawa J et al. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010;335:231–238. https://doi.org/10.1124/jpet.110.170274.

    Article  CAS  PubMed  Google Scholar 

  27. Jenkins H, Sakurai Y, Nishimura A et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41:636–648. https://doi.org/10.1111/apt.13121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sakurai Y, Nishimura A, Kennedy G et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects. Clin Transl Gastroenterol. 2015;6:e94. https://doi.org/10.1038/ctg.2015.18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial. Gastroenterology. 2022;163:608–619. https://doi.org/10.1053/j.gastro.2022.05.055.

    Article  CAS  PubMed  Google Scholar 

  30. Rokkas T, Gisbert JP, Malfertheiner P et al. Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis. Gastroenterology. 2021;161:495-507.e4. https://doi.org/10.1053/j.gastro.2021.04.012.

    Article  CAS  PubMed  Google Scholar 

  31. Graham DY, Lu H, Shiotani A. Vonoprazan-containing Helicobacter pylori triple therapies contribution to global antimicrobial resistance. J Gastroenterol Hepatol. 2021;36:1159–1163. https://doi.org/10.1111/jgh.15252.

    Article  CAS  PubMed  Google Scholar 

  32. Gisbert JP. Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review. Therap Adv Gastroenterol. 2020;13:1756284820968736. https://doi.org/10.1177/1756284820968736.

    Article  CAS  PubMed  Google Scholar 

  33. Li P, Jin J, Chen Y, Ma J, Du Q, Han Y. Susceptibility-guided vs. empirical 10-day quadruple treatment for Helicobacter pylori-infected patients: A prospective clinical trial of first-line therapy. Front Microbiol. 2022;13:973975. https://doi.org/10.3389/fmicb.2022.973975.

  34. Hsu PI, Tsai FW, Kao SS et al. Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial. Am J Gastroenterol. 2017;11:1374–1381. https://doi.org/10.1038/ajg.2017.195.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (82070551 and 81770538), the Taishan Scholars Program of Shandong Province, and the National Clinical Research Center for Digestive Diseases supporting technology project (2015BAI13B07).

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Authors and Affiliations

  1. Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, Shandong, China

    Yu-Ming Ding, Miao Duan, Zhong-Xue Han, Shu-yan Zeng, Qing-Zhou Kong, Wen-Lin Zhang, Jing Liu, Meng Wan, Min-Juan Lin, Bo-Shen Lin, Xue-ping Nan, Hui Wang, Yue-Yue Li, Xiu-Li Zuo & Yan-Qing Li

  2. Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Yu-Ming Ding, Miao Duan, Zhong-Xue Han, Shu-yan Zeng, Qing-Zhou Kong, Wen-Lin Zhang, Jing Liu, Meng Wan, Min-Juan Lin, Bo-Shen Lin, Xue-ping Nan, Hui Wang, Yue-Yue Li, Xiu-Li Zuo & Yan-Qing Li

  3. Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Yu-Ming Ding, Miao Duan, Zhong-Xue Han, Shu-yan Zeng, Qing-Zhou Kong, Wen-Lin Zhang, Jing Liu, Meng Wan, Min-Juan Lin, Bo-Shen Lin, Xue-ping Nan, Hui Wang, Yue-Yue Li, Xiu-Li Zuo & Yan-Qing Li

  4. The People’s Hospital of Jimo., Qingdao, Shandong, China

    Xiao-Hui Song

  5. Heze Municipal 3rd People’s Hospital, Heze, Shandong, China

    Feng-Lan Zhang

  6. Maternity and Child Care Health Center of Dezhou, Dezhou, Shandong, China

    Zhi Wang

  7. PKUCare Luzhong Hospital, Zibo, Shandong, China

    Zhang Ning

Authors
  1. Yu-Ming Ding
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  19. Yan-Qing Li
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Contributions

Yu-Ming Ding and Yue-Yue Li designed and planned the study. Miao Duan, Zhong-Xue Han, Xiao-Hui Song, Feng-Lan Zhang, Zhi Wang, Zhang Ning, Shu-yan Zeng, Qing-Zhou Kong, Wen-Lin Zhang, Min-Juan Lin, Bo-Shen Lin, Xue-ping Nan, and Hui Wang collected the data. Jing Liu and Meng Wan performed statistical analysis. Yu-Ming Ding prepared the original draft. Yue-Yue Li, Xiu-Li Zuo, and Yan-Qing Li supported editing of the original draft and critically revised the manuscript. All authors approved the final draft.

Corresponding author

Correspondence to Yue-Yue Li.

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The authors have no relevant financial or non-financial conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration and its later amendments. The study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (No. 2021028).

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Ding, YM., Duan, M., Han, ZX. et al. Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days. Dig Dis Sci (2024). https://doi.org/10.1007/s10620-024-08460-3

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