Comparison of Tegoprazan- and Lansoprazole-Based Fourteen-Day Triple Therapies as First-Line Treatments for <i>Helicobacter pylori</i> Eradication

Seokin Kang; Nam-Hoon Kim; Seokhyeon Jeong; Jong Wook Kim; Jung Rock Moon; Yoon Suk Lee; Jun Hyuk Son

doi:10.7704/kjhugr.2024.0012

Korean J Helicobacter Up Gastrointest Res > Volume 24(2); 2024 > Article

Kang, Kim, Jeong, Kim, Moon, Lee, and Son: Comparison of Tegoprazan- and Lansoprazole-Based Fourteen-Day Triple Therapies as First-Line Treatments for Helicobacter pylori Eradication

Original Article

The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(2):168-174.

Published online: June 10, 2024

DOI: https://doi.org/10.7704/kjhugr.2024.0012

Comparison of Tegoprazan- and Lansoprazole-Based Fourteen-Day Triple Therapies as First-Line Treatments for Helicobacter pylori Eradication

Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea

Corresponding author Nam-Hoon Kim, MD, PhD Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang 10380, Korea E-mail: n-hkim@paik.ac.kr

Received January 29, 2024; Revised March 10, 2024; Accepted March 21, 2024;

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

Tegoprazan, a novel potassium-competitive acid blocker with rapid and effective antisecretory activity, was approved for the treatment of Helicobacter pylori infections in Korea in March 2020. However, real-world data regarding tegoprazan-based therapies are scarce. We compared the efficacies of tegoprazan- and lansoprazole-based triple therapies (TTs).

Methods

Between March 2020 and February 2023, this study enrolled patients diagnosed with H. pylori infections who were prescribed either 14-day tegoprazan- or lansoprazole-based TTs as first-line treatments. Their medical records were retrospectively reviewed to compare H. pylori eradication rates and the rates of patient adherence to the recommended therapy.

Results

A total of 670 patients diagnosed with H. pylori infections were prescribed 14-day TT regimens between March 2020 and February 2023 at Ilsan Paik Hospital (Goyang, Korea). Of those enrolled in the study, 64 received tegoprazan-based TT and 295 received lansoprazole-based TT as their first-line treatment. The H. pylori eradication rates for tegoprazan- and lansoprazole-based TTs were 76.6% and 75.6%, respectively, in the intent-to-treat population; the rates were 88.9% and 88.4%, respectively, in the per-protocol population (non-inferiority test, p=0.03 and p=0.01 in the respective populations). No significant differences were observed between the two groups with regards to treatment adherence rates (84.4% vs. 85.1%, p=0.78).

Conclusions

As a first-line treatment for H. pylori eradication, 14-day tegoprazan-based TT demonstrated non-inferior efficacy compared with 14-day lansoprazole-based TT.

Key words: Helicobacter pylori; Potassium-competitive acid blockers; Proton pump inhibitors; Tegoprazan

INTRODUCTION

Helicobacter pylori is a flagellated, microaerophilic, gramnegative, spiral-shaped bacterium that colonizes the stomach. It is one of the most common human pathogens and is a significant risk factor for various gastrointestinal diseases, including gastritis, peptic ulcers, gastric cancer, and gastric mucosaassociated lymphoid tissue lymphoma, as well as extragastric diseases, such as idiopathic thrombocytopenic purpura and iron deficiency anemia [1,2]. Eradicating H. pylori infections could, therefore, potentially contribute to public health by reducing the incidence of these diseases.

Adequate acid suppression plays a crucial role in the treatment of H. pylori infections because the bacteria transition into a coccoid form at acidic pHs, rendering them resistant to antibiotics [3-5]. Moreover, maintaining a neutral intragastric pH enhances antibiotic concentrations in the gastric fluid by ensuring drug stability and reducing the minimum inhibitory concentrations (MICs) [6,7]. A 14-day triple therapy (TT) consisting of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin is one of the most widely prescribed first-line treatment regimens, worldwide, including in Korea [8].

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) that inhibits H+/K+-ATPase pumps in gastric parietal cells, similar to the action of PPIs. However, unlike PPIs, P-CABs do not require activation by gastric acid, can act on inactive H⁺/K⁺-ATPases, and remain stable at acidic pHs. Furthermore, P-CABs are less influenced by cytochrome P450 2C19 (CYP2C19). Thus, P-CABs are theoretically expected to be more rapid and effective acid blockers than PPIs [9-11]. The current Japanese guidelines recommend P-CAB-based TT as a first-line regimen [12].

In March 2020, tegoprazan was approved for the treatment of H. pylori infections in Korea. Unfortunately, limited data are available regarding tegoprazan-based therapy regimens, particularly in real-world settings. We assessed the comparative efficacies tegoprazan- and lansoprazole-based TTs as well as patient adherence to the therapeutic regimens.

METHODS

Patients

Between March 2020 and February 2023, 670 patients were diagnosed with H. pylori infections and prescribed TT regimens for the treatment of H. pylori at Ilsan Paik Hospital (Goyang, Korea). Patients were excluded from the study if they had previous histories of H. pylori eradication (59 patients), received 7- or 10-day TT regimens (176 patients), or were prescribed acid suppressants other than tegoprazan or lansoprazole (76 patients). Finally, 359 patients who received either 14-day tegoprazan-(tegoprazan group, 64 patients) or lansoprazole-based TT (lansoprazole group, 295 patients) as the first-line treatment for H. pylori infections were included in the study (Fig. 1). The patients’ baseline characteristics; main indications for H. pylori eradication; and treatment outcomes, including the results of H. pylori eradication therapy, treatment regimen adherence, and adverse events (AEs), were retrospectively investigated.

Diagnosis of H. pylori infection and confirmation of H. pylori eradication

H. pylori infections were diagnosed using one of the following tests (Supplementary Table 1 in the online-only Data Supplement): rapid urease test (Pyloplus^®; ARJ Medical, Oldsmar, FL, USA), histological examination involving modified Giemsa staining, or ¹³C-urea breath test (Otsuka Pharmaceutical, Tokyo, Japan).

Multiple national guidelines recommend the 13C-urea breath test for confirming H. pylori eradication [12-15]. Thus, patients underwent this confirmatory test at least 4 weeks after completion of the medication regimen. Breath samples were collected after the patient had fasted for at least 4 h. A tablet containing 100 mg of 13C-urea (UBIT^®; Otsuka Pharmaceutical) was administered, per os, with 100 mL of water. Follow-up breath samples were collected 20 min after the tablet had been swallowed. The presence of H. pylori was determined using the collected breath samples (Analyzer POCone; Otsuka Electronics, Osaka, Japan). The cutoff value was 2.5%.

H. pylori eradication therapy

Current Korean guidelines recommend the empirical treatment of H. pylori infections [8] with TT regimens consisting of acid suppression and two antibiotics. The tegoprazan group received tegoprazan (50 mg), amoxicillin (1000 mg), and clarithromycin (500 mg) twice daily for 14 days. The lansoprazole group received lansoprazole (30 mg), amoxicillin (1000 mg), and clarithromycin (500 mg) twice daily for 14 days. Treatment adherence was defined as the administration of at least 80% of the prescribed medications. AEs were classified into three categories: mild (symptoms subsided spontaneously), moderate (symptoms requiring management), and severe (symptoms necessitating emergency room visits).

Statistical analysis

All statistical analyses were conducted using R (Version 4.1.1; The R Foundation for Statistical Computing, Vienna, Austria). Categorical variables were analyzed using chi-square or Fisher’s exact tests, as indicated; continuous variables were analyzed using Student’s t-test or the Mann–Whitney U test. p-values <0.05 were considered statistically significant. A noninferiority test was conducted in both the intent-to-treat (ITT) and per-protocol (PP) populations; non-inferiority was declared if the lower limit of the one-sided 95% confidence interval for the difference in eradication rates was above the noninferiority margin value of -0.1.

Ethics statement

Ethics approval for this study was obtained from the Ilsan Paik Hospital Institutional Review Board (approval number 2022-10-007-001). The requirement for informed consent was waived due to the retrospective nature of the study.

RESULTS

Baseline characteristics

Table 1 presents the baseline characteristics of the 359 patients in the tegoprazan (64 patients) and lansoprazole (295 patients) groups. There were no significant differences in ages or sex distributions between the two groups. The most common indication for treatment in both groups was H. pylori-associated gastritis, followed by peptic ulcers. Adherence

Adherence and AEs

In the tegoprazan group, nine patients were lost to followup and one received insufficient medication (<80% of the prescribed medications). In the lansoprazole group, 42 patients were lost to follow-up, and two received insufficient medication (Fig. 1). Consequently, the adherence rates of the patients in the tegoprazan and lansoprazole groups were 84.4% (54/64) and 85.1% (251/295), respectively (Fig. 2); no significant difference was observed (p=0.78).

The AEs associated with tegoprazan-based TT are shown in Table 2. The overall AE rate was 23.4% (15/64). The most common AE was diarrhea (7.8%), followed by dysgeusia (6.3%). Of the 15 AEs, 14 were mild and one (patient experienced nausea and was prescribed prokinetics at a local clinic) was classified as moderate. The AEs in the lansoprazole group were unavailable due to the lack of medical records.

Outcomes

The overall H. pylori eradication rates were 75.8% (272/359) in the ITT population and 88.5% (270/305) in the PP population. In the ITT population, the H. pylori eradication rates for patients in the tegoprazan- and lansoprazole groups were 76.6% (49/64) and 75.6% (223/295), respectively (Fig. 3). The lower limit of the one-sided 95% confidence interval for the difference in eradication rates was -0.087, which was above the noninferiority margin of -10% (p=0.03). In the PP population, the eradication rates for patients in the tegoprazan- and lansoprazole groups were 88.9% (48/54) and 88.4% (222/251), respectively (Fig. 3); the lower limit of the one-sided 95% confidence interval (-0.074) was also above the non-inferiority margin of -10% (p=0.01).

DISCUSSION

P-CABs are known for their more rapid and potent acid-suppressing properties compared with PPIs. P-CABs have demonstrated superior or comparable efficacies in the treatment of various acid-related diseases, such as gastroesophageal reflux disease and peptic ulcers, for which PPIs are commonly used. In the context of H. pylori treatment, the stronger antisecretory potency of P-CABs is expected to increase antibiotic stability in the gastric fluid and reduce antibiotic MICs, thereby elevating the eradication rate [6,7,16].

Vonoprazan is a P-CAB approved and prescribed for firstline treatment of H. pylori infections in Japan [12]. Recently, a number of studies have been published regarding vonoprazan-based H. pylori eradication therapy. Even in cases involving clarithromycin-resistant H. pylori strains, vonoprazan-based TT showed an eradication rate of 82.0%, whereas the eradication rate of the comparator lansoprazole-based TT was 40.0% [17]. The strong acid suppression provided by vonoprazan appears to help TT regimens overcome the challenge of clarithromycin-resistant H. pylori strains. Furthermore, recent meta-analyses have indicated the superiority of vonoprazan-based therapy over PPIbased therapy [18-22].

In our study, the 14-day tegoprazan-based TT demonstrated H. pylori eradication rates of 76.6% and 88.9% in the ITT and PP populations, respectively. The eradication rates for the 14-day lansoprazole-based TT were 75.6% and 88.4% in the ITT and PP populations, respectively. In contrast to the reported superiority of vonoprazan for H. pylori eradication, our study failed to demonstrate the superiority of tegoprazan over lansoprazole; rather, the tegoprazan-based TT was deemed noninferior to the lansoprazole-based TT. There are several possible reasons for this finding. First, the clarithromycin MIC distribution for H. pylori may vary according to geographic region. Such differences in antibiotic resistance between the Korean and Japanese population could contribute to different efficacies. Second, the pharmacological differences between tegoprazan and vonoprazan, such as half-lives or maximum plasma concentrations, may limit the efficacy of tegoprazan. Moreover, twice daily 50-mg tegoprazan doses may be insufficient to achieve the necessary acid suppression and overcome clarithromycin resistance. A previous randomized clinical trial demonstrated that tegoprazan increases intragastric pH in a dose-dependent manner; the mean values of the 15-minute median intragastric pH over 24 h on day 7 was 5.2 with a 100-mg daily dose of tegoprazan and 6.4 with a 200-mg daily dose [23]. Therefore, increasing the tegoprazan dose to 100 mg twice daily may improve H. pylori eradication rates.

Poor therapeutic compliance is one reason for eradication failure. In our study, 1.6% and 0.7% of the patients in the tegoprazan and lansoprazole groups, respectively, received insufficient medication (<80% of the prescribed medications). Additionally, 14.1% and 14.2% of patients in the tegoprazan and lansoprazole groups, respectively, were lost to follow-up. Consequently, the adherence rates were similar for the tegoprazan (84.4%) and lansoprazole (85.1%) groups (p=0.78). Unfortunately, we were unable to investigate the AEs or other factors potentially contributing to patients being lost to follow-up due to the absence of relevant medical records.

AEs are among the most common factors leading to poor compliance. Hepatoxicity concerns were associated with the earlier P-CABs, leading to their discontinued clinical development [24]. However, vonoprazan showed similar rates of liver function abnormalities compared with lansoprazole during an 8-week treatment for erosive esophagitis, with no reported increase in hepatotoxicity during 52 weeks of maintenance therapy [25]. Furthermore, the safety profile of vonoprazan during long-term use was similar to that of lansoprazole [26]. Similarly, tegoprazan exhibited no significant difference in liver toxicity rates compared with lansoprazole, and its safety profile was similar to that of lansoprazole over a 24-week period [27]. Multiple randomized controlled trials have reported gastrointestinal disorders, including diarrhea and nausea, as the most common AEs associated with tegoprazan use, with the majority having mild intensity [27-30]. Likewise, previous studies investigating tegoprazan-based TT regimens have shown most AEs to be mild, requiring no medical management, with the most frequent ones being gastrointestinal disorders [31-34]. Our study found a 23.4% rate of AEs associated with tegoprazan-based TT, consistent with prior studies. Owing to the lack of relevant medical records, AE rates for lansoprazole-based TT could not be determined.

To date, four studies have compared tegoprazan and PPIs for the treatment of H. pylori infections [32,35-37]. Kim et al. [35] compared the efficacy of a 7-day tegoprazan-based TT regimen (tegoprazan [50 mg], clarithromycin [500 mg], amoxicillin [1000 mg]) combined with twice daily bismuth (bismuth potassium citrate [300 mg]) against a lansoprazole-based TT regimen that replaced tegoprazan with lansoprazole (30 mg). In both the ITT and PP analyses, the H. pylori eradication rates were not significantly different, consistent with our findings (78.8% vs. 74.5% with p=0.323 in the ITT analysis and 88.3% vs. 82.8% with p=0.151 in the PP analysis) [35]. However, the regimen employed by Kim et al. [35] (standard TT regimen plus bismuth) is not commonly prescribed in clinical practice and is not a recommended first-line treatment [8,12-14]. Choi et al. [32] conducted a randomized controlled trial comparing 7-day tegoprazan- and lansoprazole-based TTs. They demonstrating that tegoprazan is as effective as lansoprazole for eradicating H. pylori treatment, with eradication rates of 62.86% and 60.57%, respectively, in the ITT populations and 69.33% and 67.33%, respectively, in the PP populations. Their observed eradication rates were lower than those observed in our study. We believe that the extended 14-day treatment duration in our study contributed to the observed higher eradication rates. To improve eradication rates, the current Korean guidelines recommends 14-day TT regimens as first-line treatments [8]. In a retrospective study, Jung et al. [36] reported similar efficacies for 14-day tegoprazan- and rabeprazole-based TTs. The eradication rates of the tegoprazan- and rabeprazole-based regimens were 76.7% and 75.4%, respectively, in the ITT population and 83.4% and 83.5%, respectively, in the PP population, similar to our findings. Kim et al. [37] showed the non-inferiority of tegoprazan-based bismuth quadruple therapy to lansoprazole-based quadruple therapy as first-line H. pylori eradication treatments in a randomized controlled trial (80.0% vs. 77.4%, respectively, in the ITT analysis; 90.2% vs. 82.4%, respectively in the PP analysis). In addition, a recent retrospective study comparing tegoprazan with the combination of a PPI and an antacid for H. pylori eradication was published in 2023 [33]. It showed no significant difference in the eradication rates between 14-day tegoprazanand esomeprazole/sodium bicarbonate-based TTs (ITT population: 78.6% vs. 81.4%, respectively, p=0.313; PP population: 85.5% vs. 87.8%, respectively, p=0.339). Our study provides additional support for the non-inferior efficacy of the tegoprazan-based regimen as a first-line treatment for H. pylori eradication.

Our study had several limitations. First, this was a singlecenter retrospective observational study, which limits the generalizability of our findings. Second, the tegoprazan group had a relatively small sample size, which may have lowered the statistical power for assessing treatment efficacy. Third, adverse reactions and reasons for non-adherence were not examined due to the lack of medical records. Instead, we evaluated medication adherence and found no significant difference between tegoprazan and lansoprazole. Finally, antibiotic susceptibility tests were not performed, preventing an assessment of the efficacy of tegoprazan-based TT against clarithromycin-resistant H. pylori strains. However, we believe that the lack of antibiotic susceptibility data does not limit the clinical significance of our study as empirical therapy is commonly employed in real-world settings and continues to be recommended by guidelines [8].

In conclusion, 14-day tegoprazan-based TT was non-inferior to 14-day lansoprazole-based TT as a first-line treatment for H. pylori eradication. Thus, tegoprazan may serve as an alternative to PPIs for eradicating H. pylori.

Supplementary Materials

The online-only Data Supplement is available with this article at https://doi.org/10.7704/kjhugr.2024.0012.

Supplementary Table 1.

Methods employed for the diagnosis of Helicobacter pylori

kjhugr-2024-0012-Supplementary-Table-1.pdf

Notes

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Authors’ Contribution

Conceptualization: Seokin Kang, Nam-Hoon Kim. Data curation: all authors. Formal analysis: Seokin Kang, Nam-Hoon Kim. Methodology: Seokin Kang, Nam-Hoon Kim. Supervision: Nam-Hoon Kim, Jong Wook Kim. Writing—original draft: Seokin Kang. Writing—review & editing: Seokin Kang, Nam-Hoon Kim. Approval of final manuscript: all authors.

Acknowledgements

None

Fig. 1.

Flowchart of study enrollment. ITT, intent-to-treat; PP, per-protocol.

Fig. 2.

The adherence rates for tegoprazan- and lansoprazolebased triple therapies.

Fig. 3.

The eradication rates for tegoprazan- and lansoprazolebased triple therapies. The p-values for non-inferiority tests are indicated. ITT, intent-to-treat; PP, per-protocol.

Table 1.

Demographic and baseline characteristics of the study population

Characteristics	Tegoprazan (n=64)	Lansoprazole (n=295)	Total (n=359)	p-value
Age (yr)	56.0 (32–78)	58.0 (15–89)	57.0 (15–89)	0.45
Male	42 (65.6)	177 (60.0)	219 (61.0)	0.49
Main indication for H. pylori eradication
Peptic ulcer	14 (21.9)	79 (26.8)	93 (25.9)
EGC resected endoscopically	0 (0)	3 (1.0)	3 (0.8)
Gastric adenoma resected endoscopically	7 (10.9)	10 (3.4)	17 (4.7)
Hyperplastic polyp	4 (6.2)	3 (1.0)	7 (1.9)
Atrophic gastritis	10 (15.6)	9 (3.1)	19 (5.3)
H. pylori-associated gastritis	28 (43.8)	190 (64.4)	218 (60.7)
Others	1 (1.6)	1 (0.3)	2 (0.6)

Data are presented as median (range) or n (%).

EGC, early gastric cancer.

Table 2.

Adverse events of 14-day tegoprazan-based triple therapy

Adverse events	Value (n=64)
Any adverse events	15 (23.4)
Diarrhea	5 (7.8)
Dysgeusia	4 (6.3)
Nausea	2 (3.1)
Urticaria	1 (1.6)
Constipation	1 (1.6)
Abdominal discomfort	1 (1.6)
Headache	1 (1.6)

Data are presented as n (%).

REFERENCES

1. Crowe SE. Helicobacter pylori infection. N Engl J Med 2019;380:1158–1165.

2. de Korwin JD, Ianiro G, Gibiino G, Gasbarrini A. Helicobacter pylori infection and extragastric diseases in 2017. Helicobacter 2017;22(Suppl 1): e12411.

3. Scott D, Weeks D, Melchers K, Sachs G. The life and death of Helicobacter pylori. Gut 1998;43(Suppl 1): S56–S60.

4. Mizoguchi H, Fujioka T, Nasu M. Evidence for viability of coccoid forms of Helicobacter pylori. J Gastroenterol 1999;34(Suppl 11): 32–36.

5. Ierardi E, Losurdo G, Fortezza RF, Principi M, Barone M, Leo AD. Optimizing proton pump inhibitors in Helicobacter pylori treatment: old and new tricks to improve effectiveness. World J Gastroenterol 2019;25:5097–5104.

6. Xiong M, Bao Y, Xu X, et al. Selective killing of Helicobacter pylori with pH-responsive helix-coil conformation transitionable antimicrobial polypeptides. Proc Natl Acad Sci U S A 2017;114:12675–12680.

7. DeVault KR, Talley NJ. Insights into the future of gastric acid suppression. Nat Rev Gastroenterol Hepatol 2009;6:524–532.

8. Jung HK, Kang SJ, Lee YC, et al. Evidence-based guidelines for the treatment of Helicobacter pylori infection in Korea: 2020 revised edition. Korean J Helicobacter Up Gastrointest Res 2020;20:261–287.

9. Inatomi N, Matsukawa J, Sakurai Y, Otake K. Potassium-competitive acid blockers: advanced therapeutic option for acid-related diseases. Pharmacol Ther 2016;168:12–22.

10. Abdel-Aziz Y, Metz DC, Howden CW. Review article: potassiumcompetitive acid blockers for the treatment of acid-related disorders. Aliment Pharmacol Ther 2021;53:794–809.

11. Choi YJ. Treatment of acid-related diseases using potassium-competitive acid blockers. Korean J Gastroenterol 2022;80:247–253.

12. Kato M, Ota H, Okuda M, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 revised edition. Helicobacter 2019;24:e12597.

13. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112:212–239.

14. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022;71:1724–1762.

15. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol 2014;29:1371–1386.

16. Ahn BY, Cho SJ. Potassium-competitive acid blockers: a new therapeutic strategy for Helicobacter pylori eradication. Korean J Helicobacter Up Gastrointest Res 2023;23:174–179.

17. Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. 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 2016;65:1439–1446.

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

19. Li M, Oshima T, Horikawa T, et al. Systematic review with meta-analysis: vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori. Helicobacter 2018;23:e12495.

20. Kiyotoki S, Nishikawa J, Sakaida I. Efficacy of vonoprazan for Helicobacter pylori eradication. Intern Med 2020;59:153–161.

21. Shinozaki S, Kobayashi Y, Osawa H, et al. Effectiveness and safety of vonoprazan versus proton pump inhibitors for second-line Helicobacter pylori eradication therapy: systematic review and meta-analysis. Digestion 2021;102:319–325.

22. Lyu QJ, Pu QH, Zhong XF, Zhang J. 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;2019:9781212.

23. Han S, Choi HY, Kim YH, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of tegoprazan (CJ-12420), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther 2019;50:751–759.

24. Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Therap Adv Gastroenterol 2018;11:1756283X17745776.

25. Ashida K, Sakurai Y, Hori T, et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther 2016;43:240–251.

26. 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.

27. Cho YK, Kim JH, Kim HS, et al. Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis. Aliment Pharmacol Ther 2023;57:72–80.

28. Cho YK, Choi MG, Choi SC, et al. Randomised clinical trial: tegoprazan, a novel potassium-competitive acid blocker, or lansoprazole in the treatment of gastric ulcer. Aliment Pharmacol Ther 2020;52:789–797.

29. Kim SH, Cho KB, Chun HJ, et al. Randomised clinical trial: comparison of tegoprazan and placebo in non-erosive reflux disease. Aliment Pharmacol Ther 2021;54:402–411.

30. Lee KJ, Son BK, Kim GH, et al. Randomised phase 3 trial: tegoprazan, a novel potassium-competitive acid blocker, vs. esomeprazole in patients with erosive oesophagitis. Aliment Pharmacol Ther 2019;49:864–872.

31. Jung YS, Kim S, Kim HY, Noh SJ, Park JH, Park CH. 7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: real-world evidence. J Gastroenterol Hepatol 2022;37:1911–1918.

32. Choi YJ, Lee YC, Kim JM, et al. Triple therapy-based on tegoprazan, a new potassium-competitive acid blocker, for first-line treatment of Helicobacter pylori infection: a randomized, double-blind, phase III, clinical trial. Gut Liver 2022;16:535–546.

33. Park CH, Park JH, Jung YS. Comparative efficacy of tegoprazan vs esomeprazole/sodium bicarbonate for the treatment of Helicobacter pylori infection. Clin Transl Gastroenterol 2023;14:e00632.

34. Park CH, Song MJ, Jung BW, Park JH, Jung YS. Comparative efficacy of 14-day tegoprazan-based triple vs. 10-day tegoprazan-based concomitant therapy for Helicobacter pylori eradication. J Pers Med 2022;12:1918.

35. Kim JY, Lee SY, Kim H, Kim JH, Sung IK, Park HS. Efficacy of seven-day potassium-competitive acid blocker-based first-line Helicobacter pylori eradication therapy administered with bismuth. Yonsei Med J 2021;62:708–716.

36. Jung YS, Kim S, Kim HY, et al. Efficacy and tolerability of 14-day tegoprazan-versus rabeprazole-based triple therapy for eradication of Helicobacter pylori: a real-world evidence study. Gut Liver 2023;17:711–721.

37. Kim JS, Ko W, Chung JW, Kim TH. Efficacy of tegoprazan-based bismuth quadruple therapy compared with bismuth quadruple therapy for Helicobacter pylori infection: a randomized, double-blind, active-controlled study. Helicobacter 2023;28:e12977.