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Effectiveness and safety of vonoprazan-based regimens compared with those of proton pump inhibitor (PPI)–based regimens as first-line agents for Helicobacter pylori: a meta-analysis of randomized clinical trials

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Vonoprazan (VPZ), a reversible H+–K+ ATPase inhibitor, has a relatively fast and sustained acid-suppression action that is unaffected by diet or gene polymorphisms. Several randomized controlled trials have evaluated the difference in the eradication rate of Helicobacter pylori (HP) between VPZ-based and proton pump inhibitor (PPI)–based regimens. The present review aimed to (1) evaluate the efficacy, safety, and compliance of VPZ-based regimens compared with those of PPI-based regimens as first-line treatments for HP infection and (2) perform a subgroup analysis to examine the influence of differences in clarithromycin-resistance status, treatment duration, treatment regimens, and research region on treatment outcomes.


We conducted a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, and ChiCTR Register. Systematic searches, study selection, data extraction, risk of bias assessment, and statistical analysis were performed according to pre-registered protocol on the PROSPERO (CRD42022336608).


Eight studies and 2956 HP-infected patients were enrolled. Only first-line therapy and RCT study were considered. VPZ-based group had a superior eradication efficacy compared to PPI-based group by intention-to-treat (ITT) (pooled risk ratio (RR): 1.14, 95% CI: 1.08–1.21, p < 0.00001) and per-protocol analysis (pooled RR: 1.13, 95% CI: 1.07–1.20, p < 0.00001). This finding was further validated by subgroup analysis depending on treatment regimens, duration, region, and clarithromycin resistance. In addition, there was no significant difference in adverse events (p = 0.33) and compliances (p = 0.30) between the regimens.


The VPZ-based regimens showed a superior eradication efficacy compared to the already frequently used PPI-based regimens. Furthermore, VPZ-based therapy showed comparable tolerability and incidence of adverse events.

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Data availability

The data that support the findings of the study are available from the corresponding author on reasonable request.





Proton pump inhibitor


Helicobacter pylori


Randomized clinical trial


Risk ratios




Confidence interval


Per-protocol analysis


  1. Lee YC, Dore MP, Graham DY (2022) Diagnosis and treatment of Helicobacter pylori infection. Annu Rev Med 73:183–195.

    Article  CAS  Google Scholar 

  2. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P, Faculty members of Kyoto Global Consensus C, (2015) Kyoto global consensus report on Helicobacter pylori gastritis. Gut 64(9):1353–1367.

    Article  Google Scholar 

  3. El-Serag HB, Kao JY, Kanwal F, Gilger M, LoVecchio F, Moss SF, Crowe SE, Elfant A, Haas T, Hapke RJ, Graham DY (2018) Houston Consensus Conference on testing for Helicobacter pylori infection in the United States. Clin Gastroenterol Hepatol 16 (7):992–1002 e1006.

  4. Ang D, Koo SH, Chan YH, Tan TY, Soon GH, Tan CK, Lin KW, Krishnasamy-Balasubramanian JK, Wong YJ, Kumar R, R R, Tan Y, Ong PJ, Tan YJ, Li JW, Kwek AB, Ang TL, (2022) Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication. Aliment Pharmacol Ther.

    Article  Google Scholar 

  5. Smith SM, O’Morain C, McNamara D (2014) Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance. World J Gastroenterol 20(29):9912–9921.

    Article  CAS  Google Scholar 

  6. de Boer W, Driessen W, Jansz A, Tytgat G (1995) Effect of acid suppression on efficacy of treatment for Helicobacter pylori infection. Lancet 345(8953):817–820.

    Article  Google Scholar 

  7. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E (2018) Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 155(5):1372–1382 e1317.

  8. Bai P, Zhou LY, Xiao XM, Luo Y, Ding Y (2015) Susceptibility of Helicobacter pylori to antibiotics in Chinese patients. J Dig Dis 16(8):464–470.

    Article  CAS  Google Scholar 

  9. Sue S, Maeda S (2021) Is a potassium-competitive acid blocker truly superior to proton pump inhibitors in terms of Helicobacter pylori eradication? Gut Liver 15(6):799–810.

    Article  CAS  Google Scholar 

  10. Kiyotoki S, Nishikawa J, Sakaida I (2020) Efficacy of vonoprazan for Helicobacter pylori eradication. Intern Med 59(2):153–161.

    Article  CAS  Google Scholar 

  11. Jenkins H, Sakurai Y, Nishimura A, Okamoto H, Hibberd M, Jenkins R, Yoneyama T, Ashida K, Ogama Y, Warrington S (2015) 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 41(7):636–648.

    Article  CAS  Google Scholar 

  12. Jung YS, Kim EH, Park CH (2017) Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication. Aliment Pharmacol Ther 46(2):106–114.

    Article  CAS  Google Scholar 

  13. Yang C, Li S, Huang T, Lin H, Jiang Z, He Y, Yuan J, An H (2022) Effectiveness and safety of vonoprazan-based regimen for Helicobacter pylori eradication: a meta-analysis of randomized clinical trials. J Clin Pharm Ther.

    Article  Google Scholar 

  14. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928.

    Article  Google Scholar 

  15. Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M (2016) Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut 65(9):1439–1446.

    Article  CAS  Google Scholar 

  16. Maruyama M, Tanaka N, Kubota D, Miyajima M, Kimura T, Tokutake K, Imai R, Fujisawa T, Mori H, Matsuda Y, Wada S, Horiuchi A, Kiyosawa K (2017) Vonoprazan-based regimen is more useful than PPI-based one as a first-line Helicobacter pylori eradication: a randomized controlled trial. Can J Gastroenterol Hepatol 2017:4385161.

    Article  Google Scholar 

  17. Sue S, Ogushi M, Arima I, Kuwashima H, Nakao S, Naito M, Komatsu K, Kaneko H, Tamura T, Sasaki T, Kondo M, Shibata W, Maeda S (2018) Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: a multicenter, prospective, randomized trial. Helicobacter 23(2):e12456.

    Article  CAS  Google Scholar 

  18. Hou X, Meng F, Wang J, Sha W, Chiu CT, Chung WC, Gu L, Kudou K, Chong CF, Zhang S (2022) Vonoprazan non-inferior to lansoprazole in treating duodenal ulcer and eradicating Helicobacter pylori in Asian patients. J Gastroenterol Hepatol.

    Article  Google Scholar 

  19. Bunchorntavakul C, Buranathawornsom A (2021) Randomized clinical trial: 7-day vonoprazan-based versus 14-day omeprazole-based triple therapy for Helicobacter pylori. J Gastroenterol Hepatol 36(12):3308–3313.

    Article  CAS  Google Scholar 

  20. Zuberi BF, Ali FS, Rasheed T, Bader N, Hussain SM, Saleem A (2022) Comparison of vonoprazan and amoxicillin dual therapy with standard triple therapy with proton pump inhibitor for Helicobacter pylori eradication: a randomized control trial. Pak J Med Sci 38 (4Part-II):965–969.

  21. Chey WD, Megraud F, Laine L, Lopez LJ, Hunt BJ, Howden CW (2022) Vonoprazan triple and dual therapy for Helicobacter pylori infection in the US and Europe: randomized clinical trial. Gastroenterology.

    Article  Google Scholar 

  22. Dong SQ, Singh TP, Wei X, Yao H, Wang HL (2017) Review: a Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: is superiority an illusion? Helicobacter 22(6).

  23. Lyu QJ, Pu QH, Zhong XF, Zhang J (2019) Efficacy and safety of vonoprazan-based versus proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis of randomized clinical trials. Biomed Res Int 2019:9781212.

    Article  CAS  Google Scholar 

  24. Kato M, Ota H, Okuda M, Kikuchi S, Satoh K, Shimoyama T, Suzuki H, Handa O, Furuta T, Mabe K, Murakami K, Sugiyama T, Uemura N, Takahashi S (2019) Guidelines for the management of Helicobacter pylori infection in Japan: 2016 revised edition. Helicobacter 24(4):e12597.

  25. Graham DY, Lu H, Shiotani A (2021) Vonoprazan-containing Helicobacter pylori triple therapies contribution to global antimicrobial resistance. J Gastroenterol Hepatol 36(5):1159–1163.

    Article  CAS  Google Scholar 

  26. Liu WZ, Xie Y, Lu H, Cheng H, Zeng ZR, Zhou LY, Chen Y, Wang JB, Du YQ, Lu NH, Chinese Society of Gastroenterology CSGoHp, Peptic U (2018) Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter 23(2):e12475.

    Article  Google Scholar 

  27. Simala-Grant JL, Taylor DE (2004) Molecular biology methods for the characterization of Helicobacter pylori infections and their diagnosis. APMIS 112(11–12):886–897.

    Article  CAS  Google Scholar 

  28. Zou Y, Qian X, Liu X, Song Y, Song C, Wu S, An Y, Yuan R, Wang Y, Xie Y (2020) The effect of antibiotic resistance on Helicobacter pylori eradication efficacy: a systematic review and meta-analysis. Helicobacter 25(4):e12714.

    Article  CAS  Google Scholar 

  29. Graham DY (2017) Vonoprazan Helicobacter pylori eradication therapy: ethical and interpretation issues. Gut 66(2):384–386.

    Article  Google Scholar 

  30. 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 H, Microbiota Study G, Consensus P (2017) Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut 66(1):6–30.

    Article  Google Scholar 

  31. Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, Jones NL, Render C, Leontiadis GI, Moayyedi P, Marshall JK (2016) The Toronto Consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151(1):51–69 e14.

  32. McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP (2012) Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 36(5):414–425.

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W. L. H. was guarantor of the article. L. Y. and Y. C. S. performed the literature search with a systematic review. Y. C. S. performed the meta-analysis and extracted the data. L. Y. and Y. C. S. wrote the manuscript. And W. L. H. designed a systematic review and edited this manuscript. All authors approved the final version of this manuscript.

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Correspondence to Weiling Hu.

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Yingchao Sun and Lei Yue jointly acted as first authors of this work.

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Sun, Y., Yue, L. & Hu, W. Effectiveness and safety of vonoprazan-based regimens compared with those of proton pump inhibitor (PPI)–based regimens as first-line agents for Helicobacter pylori: a meta-analysis of randomized clinical trials. Eur J Clin Pharmacol 79, 279–288 (2023).

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