Scandinavian Journal of Gastroenterology

ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/igas20

Eradication rate and safety of vonoprazan-

amoxicillin dual therapy for helicobacter pylori
eradication: a randomized controlled trial

Guoping Jiang, Mengzhao Luo, Peifen Zheng, Yanqun Cong, Yuliang Feng &
Feng Zhou

To cite this article: Guoping Jiang, Mengzhao Luo, Peifen Zheng, Yanqun Cong, Yuliang Feng &
Feng Zhou (22 Sep 2024): Eradication rate and safety of vonoprazan-amoxicillin dual therapy
for helicobacter pylori eradication: a randomized controlled trial, Scandinavian Journal of
Gastroenterology, DOI: 10.1080/00365521.2024.2407898

To link to this article: https://doi.org/10.1080/00365521.2024.2407898

Published online: 22 Sep 2024.

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Scandinavian Journal of Gastroenterology
https://doi.org/10.1080/00365521.2024.2407898

RESEARCH ARTICLE

Eradication rate and safety of vonoprazan-amoxicillin dual therapy for

helicobacter pylori eradication: a randomized controlled trial
Guoping Jiang, Mengzhao Luo, Peifen Zheng, Yanqun Cong, Yuliang Feng and Feng Zhou
Department of Digestion, Zhejiang Hospital, Hangzhou, China

ABSTRACT ARTICLE HISTORY

Background: Helicobacter pylori (H. pylori), prevalent in developing regions, is a key factor in Received 17 July 2024
gastrointestinal diseases. Despite the common use of bismuth-based quadruple therapy, its drawbacks Revised 14 September 2024
have prompted the search for alternatives. Recently, vonoprazan, a novel acid suppressant, has shown Accepted 18 September 2024
promise in combination with antibiotics as a dual therapy for H. pylori eradication. This study aimed to KEYWORDS
assess the therapeutic outcomes and adverse events of vonoprazan-amoxicillin dual therapy compared Helicobacter pylori;
to quadruple therapy. quadruple therapy; dual
Methods: A randomized controlled trial (RCT) enrolled H. pylori-infected patients at Zhejiang Hospital. therapy; vonoprazan;
Participants were randomly assigned to dual and quadruple therapy groups. The primary endpoints high-dose amoxicillin
were H. pylori eradication and adverse events.
Results: Of the 400 patients studied from April 2022 to June 2023, In the intention-to-treat (ITT) analysis,
the eradication rates of H. pylori in vonoprazan-amoxicillin dual therapy group and quadruple therapy
group were 94.0% and 87.0%, respectively, p = 0.017. In the per-protocol (PP) analysis were 97.9% and
93.0%, p = 0.022. Additionally, the dual therapy group had a significantly lower incidence of adverse
events (19%) compared to the quadruple therapy group (53%) (p < 0.001).
Conclusion: Vonoprazan-amoxicillin dual therapy demonstrates superior eradication efficacy and
reduced adverse events compared to quadruple therapy in H. pylori-infected patients, suggesting its
potential for clinical application and promotion.

Introduction patient compliance. Notably, amoxicillin maintains a relatively

low resistance rate against H. pylori in most regions of the
Helicobacter pylori (H. pylori), a ubiquitous pathogen, affects
world, distinguishing it from other antibiotics [8,9].
approximately half of the global population, with infection As early as the 1990s, dural therapy regimens consisting
rates soaring to 80% in developing countries [1]. This bacte- of amoxicillin and proton pump inhibitors (PPIs) were
rium is a significant contributor to various digestive system reported to be used for the eradication of H. pylori, albeit
diseases, ranging from gastritis and gastric/duodenal ulcers with unsatisfactory cure rates [10,11]. This was attributed to
to gastric cancer, as well as conditions like idiopathic throm- the fact that amoxicillin’s antibacterial activity is optimal
bocytopenic purpura and unexplained iron deficiency anemia under conditions of high intragastric pH, which routine PPI
[2]. Given its prevalence and associated health risks, eradica- doses are unable to sustain [12]. However, recent studies
tion treatment is recommended for all patients infected with have demonstrated that a dual therapy regimen combining
H. pylori, barring any contraindications [3]. amoxicillin with a doubled dose of PPIs exhibits comparable
Current international guidelines advocate the use of qua- efficacy to the recommended quadruple therapy, while offer-
druple therapy containing bismuth, comprising one acid sup- ing reduced adverse events, lower costs, and improved
pressant, two antibiotics, and a bismuth agent, as the patient compliance [13,14]. Given these unique advantages,
preferred treatment for eradicating H. pylori [4–6]. However, dual therapy presents a promising avenue for future H. pylori
this therapeutic approach is associated with several limita- eradication strategies.
tions, including a higher incidence of adverse effects, ele- Vonoprazan (VPZ), a novel acid suppressant, exhibits a
vated costs, and reduced patient compliance [7]. Furthermore, competitive and reversible inhibition of H-K-ATPase with
the employment of two antibiotics in the regimen poses a potassium ions, conferring a stronger acid-suppressing effect
potential risk of future antibiotic resistance. Therefore, there than PPIs [15]. In Japan, VPZ has been approved for the treat-
is an urgent need to explore and establish novel treatment ment of gastrointestinal ulcers, reflux esophagitis, and H.
strategies for H. pylori eradication, which should aim to min- pylori eradication. Meta-analyses have consistently shown
imize antibiotic usage, reduce adverse events, and enhance that VPZ-based dual or triple therapy outperforms PPI-based

CONTACT Feng Zhou fengzz2026@163.com; Yuliang Feng fylline@sina.com Department of Digestion, Zhejiang Hospital, Hangzhou 310013, China.
© 2024 Informa UK Limited, trading as Taylor & Francis Group
2 G. JIANG ET AL.

regimens in terms of H. pylori eradication rates [16–18]. three times daily. Conversely, the control group patients were
Although VPZ has been officially listed in China, its current prescribed a treatment protocol encompassing 10 mg of
approved indication is limited to reflux esophagitis, and its rabeprazole twice daily, 1 g of amoxicillin twice daily, 500 mg
use for H. pylori eradication remains off-label. of clarithromycin twice daily, and 0.6 g of bismuth potassium
In the present study, we aimed to compare the efficacy of citrate twice daily. Both groups underwent a total treatment
VPZ-amoxicillin dual therapy with quadruple therapy in erad- duration of 14 days. Additionally, all patients were instructed
icating H. pylori. Specifically, we evaluated the eradication to refrain from alcohol consumption throughout the medica-
rate, symptom relief rate, and incidence of adverse effects tion period.
associated with both treatment regimens. Our objective was
to explore the clinical utility of VPZ and provide additional
evidence to inform future drug selection for H. pylori Observation indicators
eradication. In the present study, the principal observation indicators
encompassed the following:
Firstly, a 14 C urea breath test was conducted at least
Methods 28 days after the completion of the treatment course to con-
Participants firm the eradication of H. pylori. The eradication rate was
determined by calculating the proportion of successfully
The present study enrolled 400 patients diagnosed with H. eradicated cases to the total number of cases, expressed as a
pylori infection at Zhejiang Hospital, spanning from April percentage.
2022 to June 2023. The inclusion criteria were as follows: (1) Secondly, the occurrence of adverse events among
male or female individuals aged between 18 and 70 years; (2) patients was meticulously tracked throughout the entire
confirmed diagnosis of H. pylori infection through a 14 C urea medication period.
breath test or pathological examination; (3) never underwent
eradication therapy for H. pylori; and (4) voluntary participa-
tion in the study and provision of written informed consent. Statistical analysis
On the other hand, the exclusion criteria encompassed: (1)
Statistical analysis was performed using SPSS 23.0 software.
hypersensitivity to any medication used in this study; (2)
For measurement data adhering to a normal distribution, the
prior use of antibiotics, bismuth agents, H2-receptor antago-
mean ± standard deviation (SD) was employed as the descrip-
nists, or PPIs within one month; (3) organ insufficiency,
tive statistic. To compare the two groups, a t-test was utilized.
including liver and kidney dysfunction; (4) pregnancy or
Conversely, for measurement data violating the assumption
breastfeeding intentions among female patients; and (5) his-
of normality, the median (lower quartile, upper quartile) was
tory of upper gastrointestinal tract surgery. This study has
reported, and a rank-sum test was applied for group compar-
received approval from the Hospital Ethics Committee
ison. Counting data were summarized using frequency and
(Approval No. 2022(36K)) and registered in the China Medical
percentage, and a chi-square test was conducted for group
Research Registration System (https://www.medicalresearch.
comparison. Primary outcomes were assessed by intention-to-
org.cn, MR-33-22-003090).
treat (ITT) and per-protocol (PP) analyses. A significance level
of p < 0.05 was set for all statistical tests.
Sample size calculation
PASS 15.0 software was used for sample size calculation. The Results
power (1-β) was set at 0.9, and the significance level α was
Baseline characteristics
set at 0.05 for a two-sided test. Preliminary test results
revealed an eradication rate of 97% for the VPZ-amoxicillin A comparative analysis of demographic characteristics (age,
group and 88% for the quadruple therapy group. Based on gender, body mass index [BMI]), endoscopic diagnoses, and
these parameters and results, the minimum required sample clinical symptoms, as detailed in Table 1, failed to reveal any
size was calculated to be 175 patients per group. Taking into statistically significant differences between the two patient
account a sample loss rate ranging from 10% to 20%, the groups (p > 0.05 for all comparisons).
final selection of patients was determined to be N = 200
per group.
Eradication rates
The initial number of patients in both groups were 200.
Treatment regimens
During the treatment process, 8 patients withdrew from the
Utilizing a computer-based random number generation pro- study group due to adverse reactions, whereas 13 patients
gram, the patients enrolled in the study were randomly withdrew from the control group. Consequently, we con-
assigned to either the study group or the control group, with ducted both ITT analysis and PP analysis on the eradication
an equal distribution of 200 patients in each. The patients rate of patients. The ITT analysis revealed a notably higher
assigned to the study group received a regimen consisting of eradication rate in the study group compared to the control
20 mg of VPZ administered twice daily and 1 g of amoxicillin group, with a rate of 94.0% versus 87.0%, respectively,
 Scandinavian Journal of Gastroenterology 3

Table 1. Baseline characteristics of patients. As summarized in Table 3, the study group exhibited a sig-
Study group Control group nificantly lower overall incidence of adverse events compared
(n = 200) (n = 200) P value to the control group, with a statistically significant difference
Age 43.7 ± 15.1 44.5 ± 15.0 0.59 (p < 0.001).
Gender 0.76
Male 94 (47.0%) 98 (49.0%)
 Female 106 (53.0%) 102 (51.0%)
BMI 24.0 ± 2.2 24.1 ± 2.3 0.61 Discussion
Endoscopic diagnoses 0.66
 Chronic gastritis 75 (37.5%) 80 (40.0%) In 1989, Swiss scholars initiated a study employing a dual
Gastric ulcer 18 (9.0%) 24 (12.0%)
 Duodenal ulcer 24 (12.0%) 22(11.0%)
therapy approach, administering 40 mg of omeprazole twice
 Non invasive 83 (41.5%) 74 (37.0%) daily in conjunction with 750 mg of amoxicillin twice daily for
diagnosis a total duration of 14 days, with the aim of eradicating H.
Clinical symptoms 0.90
 Epigastric pain 31 (15.5%) 35 (17.5%)
pylori. Although the ultimate eradication rate was only 5/8,
 Abdominal distension 28 (14.0%) 29 (14.5%) this marked the initial exploration of dual therapy in this con-
 Nausea 20 (10.0%) 15 (7.5%) text [19]. Subsequently, there was a surge in dual therapy
Poor appetite 18 (9.0%) 17 (8.5%)
Belching 12 (6.0%) 16 (8.0%)
studies, but due to variations in the dosages of PPI and anti-
 Asymptomatic 91 (45.5%) 88 (44.0%) biotics employed, the eradication rates remained low.
BMI: body mass index; Study group: the vonoprazan-amoxicillin dual therapy Consequently, dual therapy was not regarded as a frontline
group; Control group: the quadruple therapy containing bismuth group. treatment option during that period. However, research
Non invasive diagnosis: diagnosed with Helicobacter pylori infection through a
14 C urea breath test, but did not undergo endoscopic examination.
efforts to develop dual therapy persisted.
In 2014, Yang et al. [20] conducted a large-scale random-
ized controlled trial, revealing that high-dose PPI dual ther-
Table 2. The H. pylori eradication rates of patients. apy, specifically 20 mg of rabeprazole combined with 750 mg
Analysis Study group Control group P value of amoxicillin, administered four times daily for 14 days, out-
ITT 94.0% (188/200) 87.0% (174/200) 0.017 performed standard regimens in both initial and rescue ther-
PP 97.9% (188/192) 93.0% (174/187) 0.022 apy for H. pylori eradication. Since then, research on high-dose
H. pylori: Helicobacter pylori; Study group: the vonoprazan-amoxicillin dual dual PPI therapy has gained momentum globally.
therapy group; Control group: the quadruple therapy containing bismuth
group. In 2022, the Chinese guideline for H. pylori eradication [21]
endorsed high-dose dual therapy, which involved either a
standard dose of PPI administered four times daily or a dou-
Table 3. The adverse events of patients. ble dose of PPI given twice daily, in combination with either
Adverse events Study group Control group P value 750 mg of amoxicillin taken four times daily or 1000 mg of
bitter taste (n, %) 7 (3.5%) 56 (28.0%) amoxicillin administered three times daily. This recommenda-
Diarrhea (n, %) 9 (4.5%) 22 (11.0%)
Nausea (n, %) 14 (7.0%) 19 (9.5%) tion was made for both initial and rescue therapy. However,
< 0.001
Skin rash (n, %) 5 (2.5%) 7 (3.5%) the study found no significant differences in eradication rates
Dizziness (n, %) 3 (1.5%) 2(1.0%) or the incidence of adverse events between patients receiv-
Total (n, %) 38 (19%) 106 (53%)
ing high-dose dual therapy and those receiving quadruple
Study group: the vonoprazan-amoxicillin dual therapy group; Control group:
the quadruple therapy containing bismuth group. therapy.
Given that VPZ exhibits a stronger acid-suppressing effect
yielding a statistically significant difference (p = 0.017). than PPI, we substituted VPZ for PPI in the high-dose dual
Furthermore, the PP analysis, which restricted the analysis to therapy. Additionally, considering patient compliance, we
patients who fully complied with the study protocol, also chose to administer amoxicillin three times daily, with each
demonstrated the eradication rate in the study group sur- dose consisting of 1 g. We compared the treatment outcomes
passed that of the control group, with respective rates of of this novel dual therapy with quadruple therapy and
97.9% and 93.0%, achieving statistical significance (p = 0.022). observed that patients treated with the former regimen
The specific data are shown in Table 2. exhibited a higher eradication rate and fewer adverse events.
Intragastric pH value serves as a crucial determinant of
antibiotic efficacy [22]. PPIs, a classically utilized acid suppres-
Adverse events sant, are known to be influenced by CYP2C19 gene polymor-
phism, leading to variabilities in drug response among
During the medication period, some patients in both groups individuals. In contrast, VPZ, a novel acid suppressant, com-
experienced adverse events. In the study group, 7 patients petitively and reversibly inhibits H-K-ATPase with potassium
reported a bitter taste, 9 experienced diarrhea, 14 com- ions. Its metabolism is less susceptible to genetic polymor-
plained of nausea, 5 developed a skin rash, and 3 exhibited phism, conferring a more robust acid-suppressing capability
dizziness, resulting in an overall adverse event incidence of compared to PPIs [23].
19%. Conversely, in the control group, 56 patients reported a In our study, we observed a higher eradication rate of H.
bitter taste, 22 experienced diarrhea, 19 complained of nau- pylori with dual therapy compared to quadruple therapy. This
sea, 7 developed a skin rash, and 2 exhibited dizziness, trans- superiority was attributed to the superior acid-suppressing
lating to an overall adverse event incidence of 53%. effect of VPZ compared to PPIs. Consistent with our findings,
4 G. JIANG ET AL.

Peng et al. [24] reported in their multicenter study that a includes two antibiotics, potentially leading to alterations in
14-day VPZ-amoxicillin dual therapy was more effective in gut microbiota compared to dual therapy [32]. It is notewor-
eradicating H. pylori than quadruple therapy. However, thy that the concurrent administration of multiple drugs
Wenhua et al. [25] did not detect a significant difference in increases the risk of adverse events.
eradication rates between VPZ-combination dual therapy and Furthermore, the Japanese guidelines recommend reduc-
quadruple therapy. We hypothesize that these differences ing the dosage of antibiotics in patients with compromised
may be attributed to variations in the studied populations. liver and kidney function [33]. Similarly, the Chinese fifth
Nonetheless, the effectiveness of dual therapy in eradicating guideline emphasizes the need for a comprehensive assess-
H. pylori is comparable to that of quadruple therapy. ment of the risks and benefits before prescribing medication
Antibiotic resistance poses a significant obstacle in the for H. pylori eradication in elderly patients [34]. Gao et al. [35]
eradication of H. pylori. The 2017 Global Priority Pathogen List demonstrated the efficacy and safety of rabeprazole-amoxicillin
of the World Health Organization (WHO) underscores the crit- dual therapy in elderly patients or those with comorbidities,
ical status of clarithromycin-resistant H. pylori, categorizing it achieving an eradication rate of 90.9% with minimal adverse
alongside methicillin-resistant Staphylococcus aureus and events. In summary, dual therapy, due to its simpler drug
vancomycin-resistant Enterococcus faecium [26]. Notably, composition, exhibits a higher safety profile compared to the
resistance rates to metronidazole and levofloxacin have also classical quadruple therapy.
significantly increased. In contrast, amoxicillin maintains a rel- The present study carried several limitations. Firstly,
atively low resistance profile [27], contributing to the high despite its status as a randomized controlled trial (RCT), the
eradication rates achieved with dual therapy, which relies absence of a blinding method could potentially introduce
solely on this antibiotic. Furthermore, amoxicillin’s bias into the results. Secondly, this study lacks drug sensitiv-
time-dependent [28] nature enhances its efficacy when ity testing, which may have some impact on the results.
administered three times daily, outperforming the traditional Thirdly, the study’s scope was confined to patients from
twice-daily regimen employed in quadruple therapy. As the Zhejiang Hospital, thereby limiting the generalizability of the
sole antibiotic in dual therapy, amoxicillin exerts minimal findings to other hospitals in the study area or across differ-
impact on the development of subsequent antibiotic ent regions of China. To further validate our findings, future
resistance. research endeavors should strive towards conducting RCTs
The selection of optimal antibiotics for H. pylori eradica- with a larger scale, multi-center design, and the inclusion of
tion necessitates meticulous consideration, with preference double-blinding methods.
given to those exhibiting lower resistance rates based on
drug sensitivity testing. However, the invasive nature of H.
pylori susceptibility testing, coupled with the requirement for Conclusion
laboratory cell culture, poses practical challenges and ele- In conclusion, our study has corroborated that the dual ther-
vates medical costs, thereby limiting its routine clinical appli- apy consisting of VPZ-amoxicillin exhibits a superior eradica-
cation [29]. Consequently, international consensus generally tion rate and enhanced safety profile in comparison to the
advises against routine H. pylori susceptibility testing prior to traditional quadruple therapy. Despite the fact that the latest
initial eradication therapy [30]. The results of our study indi- Chinese guidelines have yet to recognize it as a standard
cate that dual therapy, utilizing a single antibiotic, achieves treatment for eradicating H. pylori, its distinct advantages
superior eradication rates compared to traditional quadruple suggest that it deserves consideration for widespread appli-
therapy, suggesting its potential as a first-line treatment cation in China in the future.
option for H. pylori infection. In cases where dual therapy
fails, a tailored combination therapy incorporating multiple
antibiotics, guided by drug sensitivity data, can serve as an Authors’ contributions
effective salvage therapy. This approach minimizes unneces-
FZ and YLF conceptualized and designed the study. PFZ and YQC col-
sary antibiotic exposure, thereby mitigating the risk of wide-
lected all relevant data of patients, GPJ and MZL analyzed data, and
spread drug resistance and reducing healthcare costs. drafted and revised the manuscript. All authors had full access to the
The issue of safety during medication holds significant data, contributed to the study, approved the final version for publication,
importance in the context of eradicating H. pylori. The occur- and take responsibility for its accuracy and integrity.
rence of adverse events associated with medication must be
carefully considered. In our study, the most prevalent adverse
event observed was a bitter taste, primarily manifesting in Disclosure statement
the quadruple therapy group. This can be attributed to the No potential conflict of interest was reported by the author(s).
well-known side effect of bismuth agents, as highlighted by
Cheng et al. [31] in their randomized trial, where 60.4% of
patients receiving quadruple therapy reported experiencing Ethics approval
symptoms of bitter taste. Additionally, diarrhea emerged as
This study has received approval from the Hospital Ethics Committee
the second most frequent adverse event in our study, with a (Approval No. 2022(36K)) and registered in the China Medical Research
higher incidence in the quadruple therapy group. This is Registration System (https://www.medicalresearch.org.cn, MR-33-22-
likely due to the quadruple therapy’s composition, which 003090).
 Scandinavian Journal of Gastroenterology 5

Funding [18] Lyu Q-J, Pu Q-H, Zhong X-F, et al. Efficacy and safety of
vonoprazan-based versus proton pump inhibitor-based triple ther-
This study was supported by the Medical Science and Technology Project apy for helicobacter pylori eradication: a meta-analysis of random-
of Zhejiang Province (No. 2022KY013). ized clinical trials. Biomed Res Int. 2019;2019:9781212–9781218.
doi:10.1155/2019/9781212.
[19] Unge P, Gad A, Gnarpe H, et al. Does omeprazole improve antimi-
References crobial therapy directed towards gastric Campylobacter pylori in
[1] Leja M, Axon A, Brenner H. Epidemiology of helicobacter pylori in- patients with antral gastritis? A pilot study. Scand J Gastroenterol
fection. Helicobacter. 2016;21(S1):3–7. doi:10.1111/hel.12332. Suppl. 1989;167:49–54. doi:10.3109/00365528909091311.
[2] Crowe SE. Helicobacter pylori infection. N Engl J Med. [20] Yang J-C, Lin C-J, Wang H-L, et al. High-dose dual therapy is supe-
2019;380(12):1158–1165. doi:10.1056/NEJMcp1710945. rior to standard first-line or rescue therapy for Helicobacter pylori
[3] Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report infection. Clin Gastroenterol Hepatol. 2015;13(5):895–905 e5.
on helicobacter pylori gastritis. Gut. 2015;64(9):1353–1367. doi:10.1016/j.cgh.2014.10.036.
doi:10.1136/gutjnl-2015-309252. [21] Zhou L, Lu H, Song Z, et al. 2022 Chinese national clinical practice
[4] Malfertheiner P, Megraud F, O'Morain CA, et al. Management of guideline on Helicobacter pylori eradication treatment. Chin Med J
helicobacter pylori infection-the maastricht v/florence consensus (Engl). 2022;135(24):2899–2910. doi:10.1097/CM9.0000000000002546.
report. Gut. 2017;66(1):6–30. doi:10.1136/gutjnl-2016-312288. [22] McNicholl AG, Linares PM, Nyssen OP, et al. Meta-analysis: esome-
[5] Chey WD, Leontiadis GI, Howden CW, et al. Correction: ACG clinical prazole or rabeprazole vs. first-generation pump inhibitors in the
guideline: treatment of helicobacter pylori infection. Am J treatment of Helicobacter pylori infection. Aliment Pharmacol Ther.
Gastroenterol. 2018;113(7):1102. doi:10.1038/s41395-018-0132-6. 2012;36(5):414–425. doi:10.1111/j.1365-2036.2012.05211.x.
[6] Fallone CA, Chiba N, van Zanten SV, et al. The toronto consensus [23] Sakurai Y, Mori Y, Okamoto H, et al. Acid-inhibitory effects of vono-
for the treatment of helicobacter pylori infection in adults. prazan 20 mg compared with esomeprazole 20 mg or rabeprazole
Gastroenterology. 2016;151(1):51–69 e14. doi:10.1053/j.gas- 10 mg in healthy adult male subjects–a randomised open-label
tro.2016.04.006. cross-over study. Aliment Pharmacol Ther. 2015;42(6):719–730.
[7] Graham DY, Dore MP, Lu H. Understanding treatment guidelines doi:10.1111/apt.13325.
with bismuth and non-bismuth quadruple Helicobacter pylori [24] Peng X, Chen H-W, Wan Y, et al. Combination of vonoprazan and
eradication therapies. Expert Rev Anti Infect Ther. 2018;16(9):679– amoxicillin as the first-line Helicobacter pylori eradication therapy:
687. doi:10.1080/14787210.2018.1511427. a multicenter, prospective, randomized, parallel-controlled study.
[8] Gao W, Cheng H, Hu F, et al. The evolution of Helicobacter pylori Clin Exp Med. 2023;23(7):4011–4019. doi:10.1007/s10238-023-
antibiotics resistance over 10 years in Beijing, China. Helicobacter. 01074-5.
2010;15(5):460–466. doi:10.1111/j.1523-5378.2010.00788.x. [25] Wenhua J, Zhaohui H. Clinical comparison between improved
[9] Li S-Y, Li J, Dong X-H, et al. The effect of previous eradication fail- double regimen and standard quadruple regimen for Helicobacter
ure on antibiotic resistance of Helicobacter pylori: A retrospective pylori. Chin J Gastrointest Endosc. 2023;10(02):103–108.
study over 8 years in Beijing. Helicobacter. 2021;26(4):e12804. [26] Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and
doi:10.1111/hel.12804. development of new antibiotics: the WHO priority list of antibiotic-
[10] Koizumi W, Tanabe S, Hibi K, et al. A prospective randomized study resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–
of amoxycillin and omeprazole with and without metronidazole in 327. doi:10.1016/S1473-3099(17)30753-3.
the eradication treatment of Helicobacter pylori. J Gastroenterol [27] Ierardi E, Giorgio F, Losurdo G, et al. How antibiotic resistances could
Hepatol. 1998;13(3):301–304. doi:10.1111/j.1440-1746.1998.01559.x. change Helicobacter pylori treatment: A matter of geography? World J
[11] Wong, B C, Xiao, S D, Hu, F L, et al., Comparison of lansoprazole- Gastroenterol. 2013;19(45):8168–8180. doi:10.3748/wjg.v19.i45.8168.
based triple and dual therapy for treatment of Helicobacter [28] Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics
pylori-related duodenal ulcer: an Asian multicentre double-blind of antibacterial agents. Infect Dis Clin North Am. 2009;23(4):791–
randomized placebo controlled study. Aliment Pharmacol Ther, 815. doi:10.1016/j.idc.2009.06.008.
2000. 14(2):217–24. doi:10.1046/j.1365-2036.2000.00689.x. [29] O'Morain C, Smith SM. Antimicrobial susceptibility testing for
[12] Graham DY, Lu H, Dore MP. Relative potency of proton-pump in- Helicobacter pylori comes of age. Lancet Gastroenterol Hepatol.
hibitors, helicobacter pylori therapy cure rates, and meaning of 2023;8(7):593–595. doi:10.1016/S2468-1253(23)00113-9.
double-dose PPI. Helicobacter. 2019;24(1):e12554. doi:10.1111/ [30] Gisbert JP. Empirical or susceptibility-guided treatment for
hel.12554. Helicobacter pylori infection? A comprehensive review. Therap Adv
[13] Gao C-P, Zhang D, Zhang T, et al. PPI-amoxicillin dual therapy for Gastroenterol. 2020;13:1756284820968736. doi:10.1177/17562848
helicobacter pylori infection: An update based on a systematic re- 20968736.
view and meta-analysis. Helicobacter. 2020;25(4):e12692. [31] Cheng J, Fan C, Huang K, et al. Efficacy and safety of high-dose
doi:10.1111/hel.12692. ilaprazole-amoxicillin dual therapy for Helicobacter pylori eradica-
[14] Zhu Y-J, Zhang Y, Wang T-Y, et al. High dose PPI-amoxicillin dual tion: a prospective, single-center, randomized trial. Front Pharmacol.
therapy for the treatment of Helicobacter pylori infection: a sys- 2023;14:1272744. doi:10.3389/fphar.2023.1272744.
tematic review with meta-analysis. Therap Adv Gastroenterol. [32] Horii T, Suzuki S, Takano C, et al. Lower impact of vonoprazan-
2020;13:1756284820937115. doi:10.1177/1756284820937115. amoxicillin dual therapy on gut microbiota for Helicobacter pylori
[15] Yang X, Li Y, Sun Y, et al. Vonoprazan: a novel and potent alterna- eradication. J Gastroenterol Hepatol. 2021;36(12):3314–3321.
tive in the treatment of acid-related diseases. Dig Dis Sci. doi:10.1111/jgh.15572.
2018;63(2):302–311. doi:10.1007/s10620-017-4866-6. [33] Kato M, Ota H, Okuda M, et al. Guidelines for the management of
[16] Sun Y, Yue L, Hu W. Effectiveness and safety of vonoprazan-based Helicobacter pylori infection in Japan: 2016 Revised Edition.
regimens compared with those of proton pump inhibitor (PPI)- Helicobacter. 2019;24(4):e12597. doi:10.1111/hel.12597.
based regimens as first-line agents for Helicobacter pylori: a [34] Liu WZ, Xie Y, Lu H, et al. Fifth Chinese national consensus report
meta-analysis of randomized clinical trials. Eur J Clin Pharmacol. on the management of helicobacter pylori infection. Helicobacter.
2023;79(2):279–288. doi:10.1007/s00228-022-03430-y. 2018;23(2):e12475. doi:10.1111/hel.12475.
[17] Rokkas T, Gisbert JP, Malfertheiner P, et al. Comparative effectiveness [35] Gao W, Ye H, Deng X, et al. Rabeprazole-amoxicillin dual therapy
of multiple different first-line treatment regimens for helicobacter as first-line treatment for H pylori eradication in special patients: A
pylori infection: a network meta-analysis. Gastroenterology. retrospective, real-life study. Helicobacter. 2020;25(5):e12717.
2021;161(2):495–507 e4. doi:10.1053/j.gastro.2021.04.012. doi:10.1111/hel.12717.