Efficacy and safety of triple therapy with vonoprazan for Helicobacter pylori eradication: A multicenter, prospective, randomized controlled trial

Abstract

BACKGROUND

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach, damaging the gastric mucosa through various mechanisms and leading to various digestive disorders. Accurate assessment and precise treatment are essential in initial intensive therapy.

AIM

To investigate the efficacy and safety of a vonoprazan (VPZ)-based triple regimen for first-line eradication of H. pylori in China.

METHODS

This multicenter noninferior randomized controlled trial (June 2022 to November 2023) involved 524 H. pylori-positive patients across 19 centers in Shandong, China. Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC), 14-day VPZ/amoxicillin/clarithromycin (VACa), or 10-day VPZ/amoxicillin/clarithromycin (VACb) - all administered twice daily. Primary outcomes (eradication rates) were assessed via intention-to-treat (ITT) and per-protocol (PP) analyses. Secondary endpoints included adverse events and adherence. Noninferiority testing and χ² tests were used for statistical comparisons.

RESULTS

A total of 524 patients participated in this study. In ITT analysis, the eradication rates of the EBAC, VACa, and VACb groups were 72.6% (127/175), 88.0% (154/175), and 83.3% (145/174), respectively (P = 0.001). The difference in the eradication rate between the EBAC and VPCa groups was 15.4% [95% confidence interval (CI): 7.3-23.6, P < 0.001], and that between the EBAC and VACb groups was 10.8% (95%CI: 2.1-19.4, P = 0.018). In PP analysis, the eradication rates of the EBAC, VACa, and VACb groups were 81.4% (127/156), 93.9% (154/164), and 90.6% (145/160), respectively (P = 0.001). There was no significant difference in the incidence of adverse reactions among the three groups, which were 36.6%, 33.8% and 29.6%, respectively (P = 0.50).

CONCLUSION

VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens, with the 10-day regimen showing comparable efficacy and similar adverse event rates.

Key Words: Helicobacter pylori; Vonoprazan triple therapy; Potassium-competitive acid blockers; Eradication rate; First-line therapy

Core Tip: This multicenter randomized controlled trial pioneered a head-to-head comparison of vonoprazan (VPZ)-based triple therapy (VPZ/amoxicillin/clarithromycin) against China’s standard 14-day bismuth quadruple regimen esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC), while evaluating a novel 10-day VPZ regimen. Among 524 treatment-naïve patients, VPZ triple therapy demonstrated superior eradication rates vs EBAC in intention-to-treat and per-protocol analyses, achieving noninferiority thresholds. Adverse event incidence remained comparable, with the 10-day regimen showing the lowest rate. These findings establish VPZ triple therapy as an effective bismuth-free alternative, validating abbreviated 10-day regimens to enhance compliance without compromising efficacy.

INTRODUCTION

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach, damaging the gastric mucosa through various mechanisms and leading to various digestive disorders. A recent study found that the global prevalence of adults infected with H. pylori was 43.9%[1]. Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%[2]. Numerous studies have shown that eradicating H. pylori can improve the gastric environment and reduce the risk of gastric cancer, gastric ulcers, gastric mucosa-associated tissue lymphoma, and other gastrointestinal diseases[3,4].

Currently, 14-day bismuth quadruple therapy is the first-line regimen for H. pylori eradication in China, consisting of a combination of a proton pump inhibitor (PPI), bismuth, and two antibiotics, with an average eradication rate of 81.3%[5]. The metabolism of most PPIs is primarily mediated by cytochrome P450 (CYP) 2C19. Polymorphisms in this enzyme contribute to interindividual variability in therapeutic outcomes, particularly with first-generation agents such as omeprazole, where CYP2C19 genotype significantly influences drug exposure and acid-suppression efficacy[6]. Esomeprazole, the S-isomer of omeprazole, demonstrates improved bioavailability and a prolonged duration of acid suppression. Its pharmacokinetic profile is characterized by reduced first-pass metabolism and decreased CYP2C19-mediated hydroxylation, which are associated with its superior acid-suppressive efficacy compared to racemic omeprazole[7]. A meta-analysis of 17 studies indicated that the best first-line treatment for H. pylori is using acid inhibitors that are not dependent on CYP2C19 polymorphisms[8]. The 14-day bismuth-containing quadruple regimen has a high incidence of adverse events, various medications, and poor medication compliance, and there is an urgent need for an alternative to optimize the treatment regimen for H. pylori.

Vonoprazan (VPZ) is a novel potassium-competitive gastric acid blocker that rapidly inhibits gastric acid secretion by reversibly inhibiting H⁺/K⁺-ATPase from binding to K⁺ and preventing H⁺ from entering the gastric lumen[9]. VPZ is mainly metabolized by CYP3A4 and is not affected by CYP2C19 polymorphism. VPZ was first approved for eradicating H. pylori in Japan in 2015[10]. In 2020, the Japanese Society of Gastroenterology revised the third edition of its Evidence-Based Clinical Practice Guidelines for Peptic Ulcer Disease. The guidelines recommended VPZ in combination with antibiotics as the first-line treatment for eradicating H. pylori[11]. Most studies have demonstrated that VPZ-based regimens are safe and effective in eradicating H. pylori, and the first-line eradication rates for the efficacy of the triple regimen composed of VPZ, amoxicillin, and clarithromycin (VAC) are satisfactory[12-16]. A recent meta-analysis that included 27 randomized controlled trials found that the eradication rates of VPZ-based bismuth quadruple therapy and triple therapy (VAC) were > 90% based on PP analysis[17].

At present, most research on VPZ has been conducted in Japan. Considering the unavailability of bismuth in Japan, studies comparing the VPZ triple regimen group with the bismuth quadruple regimen group are limited. Thus, more data are necessary to support the efficacy and safety of the VPZ regimen in China. Current guidelines and consensus have not yet demonstrated the efficacy and safety of a shortened VPZ triple regimen, but it has been shown that a high eradication rate can still be achieved with a 7-day VPZ triple therapy[18]. Our recent multicenter clinical trial in China showed that for the quadruple therapy based on VPZ, in PP analysis, the eradication rates of 10-day and 14-day treatment courses were 91.5% [95% confidence interval (CI): 88.53%-94.46%] and 92.11% (95%CI: 88.99-95.29%), respectively, with no significant difference (P = 0.772). The incidence of adverse reactions was lower in the 10-day treatment group (P = 0.023). Currently, no studies have compared the triple regimen of VPZ with the standard bismuth quadruple regimen. Therefore, this study aimed to investigate the efficacy and safety of the 14-day VPZ triple regimen and the shortened 10-day regimen in the Chinese population.

MATERIALS AND METHODS

Study design and ethical issues

This was a multicenter, prospective, open-label, randomized controlled trial conducted between June 2022 and November 2023 at 19 clinical trial centers in Shandong Province. The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (No. QFYKYLL 916411920) and the Ethics Committees of all participating centers, and all patients provided informed consent. This study was conducted in accordance with the principles of the CONSORT statement on randomized controlled trials and was registered on ClinicalTrials.gov (registration number: ChiCTR2200061000).

Patient selection

H. pylori-positive patients aged 18-75 years were recruited.

The inclusion criteria: (1) Aged 18-75 years; (2) Presence of H. pylori infection proven by positivity of any one of the C13 or C14 breath test, rapid urease test, or histopathology; (3) No history of eradication therapy for H. pylori infection; (4) No history of allergy to the medicines in the study protocol; and (5) written informed consent.

The exclusion criteria: (1) Active gastrointestinal bleeding; (2) History of upper gastrointestinal surgery; (3) Pregnant and lactating women and those unwilling to use contraception during the trial period; (4) Concurrent presence of other serious illnesses that would affect evaluation of the study, such as severe liver disease, lung disease, heart disease, kidney disease, or malignant tumors; (5) History of allergy to the test drug; and (6) Treated for H. pylori once or more.

Dropout criteria: (1) Loss to follow-up or voluntary dropout from the trial; (2) Unintended pregnancy; (3) Intolerable adverse events; and (4) Reasons for dropout as determined by the investigator.

Randomization and treatment

H. pylori-positive patients were randomly assigned to receive a 14-day esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC) or VAC regimen (10 or 14 days). At the beginning of the experiment, computer-generated random number sequences were used to randomly divide eligible patients into three groups at a ratio of 1:1:1. Randomized grouping concealment used opaque and sealed envelopes labeled with the subject numbers. The intervention was carried out in accordance with the grouping scheme inside the envelope. The control group was given esomeprazole 20 mg + bismuth potassium citrate 220 mg + amoxicillin 1000 mg + clarithromycin 500 mg for 14 days (EBAC group). The following experimental groups were given VPZ-based triple therapy: VPZ 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg for 14 days (VACa group); or VPZ 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg for 10 days (VACb group). All drugs were given twice daily in all treatment protocols. The physicians administering the urea breath test (UBT) were single-blinded to treatment allocation. To ensure equitable participation, all study medications were supplied at no cost, funded through research grants.

Sample size calculation

Based on previous reviews and meta-analyses, the H. pylori eradication rate of VPZ triple therapy (VAC) was approximately 90%[19]. We assumed that the eradication rate of EBAC was 78% and that of VAC was 90%[20-22]. A noninferiority study was used, assuming a power of 85%, unilateral alpha of 0.025, a noninferior margin of 10%, and an allocation ratio of 1:1:1 among the three groups, with a total sample size of 471 subjects (157 in each group) calculated by PASS 2021 software. Considering that 10% of the subjects may be lost to follow-up, the total sample size should be 519 cases (173 cases in each group).

Statistical analysis

Patients performed 13C/14C-UBT 4-6 weeks after completion of treatment. Taking < 80% of the total dose was considered poor adherence. Not returning for a 13C (or 14C) UBT review was considered failure to follow-up. The eradication rates, treatment-related adverse events, and adherence to the three regimens were compared. The primary endpoint was the noninferiority of the VAC vs the EBAC group, with a noninferiority margin of 10%. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to investigate the eradication rate between the two groups. ITT analysis included all patients participating in the study; PP analysis excluded all patients who violated the study protocol. All demographic information, frequency of adverse reactions, and patient review results were documented. Analysis of variance or the Wilcoxon rank-sum test was used to compare differences in quantitative data between the two groups, which were described as mean ± SD, and the χ² test was conducted to compare the frequency distributions of differences in eradication rates, incidence of adverse events, and adherence among the three groups. The 95%CI was calculated to determine the difference in eradication rates among the groups. Data analysis was performed using SPSS 26.0.

RESULTS

Baseline characteristics of the participants

From June 2022 to November 2023, 545 patients were evaluated, and 524 patients were enrolled (Figure 1). After excluding subjects who were lost to follow-up, tolerated adverse events, had poor compliance, or violated the protocol, 476 were included in PP analysis. No significant difference in the rates of incomplete studies and loss to follow-up was found among the three groups (P = 0.268). The final follow-up ended on November 9, 2023. No significant difference in baseline characteristics was found (all P > 0.05; Table 1).

Figure 1 CONSORT flowchart showing the progress of the trial. ITT: Intention-to-treat; mITT: Modified intention-to-treat; PP: Per protocol; EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin.

Table 1 Baseline characteristics and demographics, n (%).

Characteristics	EBAC group (n = 175)	VACa group (n = 175)	VACb group (n = 174)
Age (year), mean ± SD	47.27 ± 11.48	48.20 ± 11.65	47.21 ± 11.70
Female sex	82 (46.9)	91 (52.0)	94 (54.0)
Married	170 (97.1)	162 (92.6)	161 (92.5)
Weight (kg), mean ± SD	68.36 ± 10.40	67.03 ± 10.95	66.74 ± 10.31
Height (cm), mean ± SD	168.18 ± 8.44	167.41 ± 7.49	167.36 ± 8.49
BMI, mean ± SD	24.12 ± 2.94	23.82 ± 2.85	23.78 ± 2.81
Smoking	19 (10.9)	14 (8.0)	16 (9.2)
Alcohol intake	54 (30.9)	43 (24.6)	46 (26.4)
High blood pressure	26 (14.9)	22 (12.6)	13 (7.5)
Diabetes	9 (5.1)	8 (4.6)	4 (2.3)
Family history of gastric cancer	14 (8.0)	9 (5.1)	6 (3.4)
History of peptic ulcer
No peptic ulcers	164 (93.7)	166 (94.9)	169 (97.1)
Gastric ulcer	5 (2.9)	7 (4.0)	4 (2.3)
Duodenal ulcer	6 (3.4)	2 (1.1)	1 (0.6)
Helicobacter pylori infection in family members	57 (32.6)	47 (26.9)	57 (32.8)

BMI: Body mass index; EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin.

H. pylori eradication rates

In ITT analysis, the eradication rate was 72.6% (127/175) in the EBAC group, 88.0% (154/175) in the VACa group, and 83.3% (145/174) in the VACb group. PP analysis was performed on all patients who completed the study. The eradication rate was 81.4% (127/156) in the EBAC group, 93.9% (154/164) in the VACa group, and 90.6% (145/160) in the VACb group. In ITT and PP analyses, the difference in eradication rates between the VACa and VACb groups was not significant (P = 0.213, P = 0.269; Figure 2 and Table 2).

Figure 2 Comparison of eradication rates in the groups. ITT: Intention-to-treat; mITT: Modified intention-to-treat; PP: Per protocol; EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin.

Table 2 Difference in eradication rates of each therapy group.

	EBAC	VACa	VACb	P value	χ2
ITT (%)	72.6	88.0	83.3	0.001	14.409
95%CI	66.0-79.2	83.2-92.8	77.8-88.9
n	127/175	154/175	145/174
PP (%)	81.4	93.9	90.6	0.001	13.341
95%CI	75.3-87.5	90.2-97.6	86.1-95.1
n	127/156	154/164	145/160

EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin; CI: Confidence interval; ITT: Intention-to-treat; PP: Per-protocol.

Rates of adverse events and compliance

In analyzing the incidence of adverse events, 52 patients in the EBAC group reported drug-related adverse events, and the incidence of adverse events in the three groups was 36.6%, 33.8%, and 29.6%, respectively (P = 0.50). Common adverse events included nausea, dizziness, diarrhea, and decreased appetite, which are all resolved independently at the end of treatment. One patient in the EBAC group was reported to have gastrointestinal bleeding during H. pylori eradication therapy. He was diagnosed with a duodenal ulcer after endoscopy and was hospitalized after termination of the trial (Table 3).

Table 3 Adverse events and patient compliance, n (%).

Adverse events	EBAC group (n = 175)	VACa group (n = 175)	VACb group (n = 174)	P value
Constipation	22 (12.6)	17 (9.7)	12 (6.9)
Diarrhea	9 (5.1)	10 (5.7)	9 (5.2)
Headache	7 (4.0)	5 (2.9)	7 (4.0)
Bitter/abnormal taste	3 (1.7)	5 (2.9)	2 (1.1)
Nausea	6 (3.4)	4 (2.3)	5 (2.9)
Bloating/indigestion	3 (1.7)	1 (0.6)	3 (1.7)
Anorexia	1 (0.6)	5 (2.9)	1 (0.6)
Gastrointestinal hemorrhage	1 (0.6)	1 (0.6)	3 (1.7)
Total	52 (36.6)	48 (33.8)	42 (29.6)	0.5
Unfinished studies	19 (10.9)	11 (6.3)	14 (8.0)	0.298

EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin.

Comparison of noninferiority

The eradication rates of the 10-day and 14-day VAC regimens were > 80% based on ITT analysis and > 90% based on PP analysis. The lower limit of the 95%CI for the difference in eradication rates of VAC was above the expected noninferiority boundary in ITT and PP analyses, indicating that neither VACa nor VACb was inferior to EBAC (Table 4).

Table 4 Noninferiority analysis of Helicobacter pylori eradication rates.

	VACa	VACb
Differences from the EBAC group in ITT analysis	15.4	10.8
95%CI for difference	7.3-23.6	2.1-19.4
Noninferior P value	< 0.001a	0.018a
Differences from EBAC group in PP analysis	12.5	9.2
95%CI for difference	5.4-19.6	1.6-16.8
Noninferior P value	0.001a	0.014a

^aP < 0.025.

EBAC: Esomeprazole/bismuth/amoxicillin/clarithromycin; VACa: 14-day vonoprazan/amoxicillin/clarithromycin; VACb: 10-day vonoprazan/amoxicillin/clarithromycin; CI: Confidence interval; ITT: Intention-to-treat; PP: Per-protocol.

DISCUSSION

The overall H. pylori eradication rate of the VPZ-based triple regimen was acceptable, and was noninferior to the empirical bismuth quadruple group in both the ITT and PP analyses, and the eradication rate was > 90% in both PP analyses. We compared the efficacy of the 10-day vs 14-day VAC regimen, and no significant difference in eradication rates was found between the two groups, which were superior to those of the traditional first-line quadruple regimen. This indicates that a shorter VPZ treatment duration can still achieve satisfactory eradication rates, and further large-scale clinical trials are necessary to demonstrate the feasibility of the 10-day VPZ regimen in the Chinese population, optimize clinical treatment, and reduce the burden of drug use. To the best of our knowledge, this is the first prospective study to evaluate the efficacy and safety of a 10-day VPZ triple regimen as a first-line treatment for H. pylori infection (Figure 3).

Figure 3 Design of this multicenter, prospective, randomized controlled trial. ITT: Intention-to-treat; PP: Per protocol.

Multiple studies have reported pharmacokinetic, pharmacological, and safety data of VPZ. A study comparing VPZ and lansoprazole showed that the proportion of intragastric pH > 4 was three times greater 24 hours after a single dose of VPZ and two times greater 1 week later[23]. Jenkins et al[24] concluded that the acid-suppressive effects of VPZ were faster, more profound, and longer lasting regardless of region, and that VPZ was well tolerated in the dose range of 20-120 mg, making it a potential alternative to PPIs for the treatment of acid-related diseases. Murakami et al[25] noted that a first-line triple regimen of VPZ increased the H. pylori eradication rate in extensive metabolizers of CYP2C19. A phase 4 randomized, single-blind, single-center trial reported a higher eradication rate in the VPZ group than in the PPI group based on PP analysis (95.7% vs 71.4%, P = 0.0002, 95%CI: 88.0%-99.1% vs 58.7%-82.1%)[12]. Another Japanese review, including six prospective and 12 retrospective studies, had similar conclusions, with an eradication rate of approximately 90% with the VPZ triple regimen, and the incidence of adverse events was not significantly different from that of the PPI group[21]. Another net meta-analysis that included 68 randomized controlled trials comparing the efficacy of different treatment regimens and the effectiveness ranking showed that VPZ triple therapy was the most effective, with an eradication rate > 90%[19].

Most PPIs act on CYP2C19, influencing H. pylori eradication and treatment effectiveness. Based on genetic polymorphisms, CYP2C19 metabolic phenotypes can be categorized into five groups: Ultra-rapid metabolizer, rapid metabolizer, normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM). Studies have shown that individuals with the PM genotype have higher H. pylori eradication rates compared to those with IM or NM genotypes[26]. Given its reduced sensitivity to CYP2C19 variability, esomeprazole was selected as the positive control in this study and demonstrated superior H. pylori clearance. However, due to interethnic and individual genetic differences, genotyping of CYP2C19 is recommended when feasible, to optimize personalized treatment strategies for H. pylori eradication. Unlike traditional PPIs, VPZ is mainly metabolized by CYP3A4, reducing the impact of CYP2C19 polymorphisms. CYP3A4 is a key hepatic enzyme with broad substrate specificity, and drug-drug interactions involving CYP3A4 can alter metabolic activity, potentially increasing plasma drug concentrations[27]. Clarithromycin (a CYP3A4 inhibitor) co-administered with VPZ increases plasma concentrations of both, although not clinically significantly[28]. VPZ-containing regimens also show efficacy against clarithromycin-resistant strains, possibly due to enhanced antibiotic activity from potent acid suppression[29]. CYP3A4-mediated interactions also extend to statins such as atorvastatin, which is administered in its hydroxyacid form and metabolized to an inactive lactone. Co-administration with VPZ significantly increases systemic exposure to atorvastatin lactone, suggesting VPZ-mediated inhibition of CYP3A4 and a potential elevation in the risk of muscle-related adverse events, such as myopathy[30]. VPZ affects the metabolism of midazolam, a commonly used sedative also metabolized by CYP3A4. In animal studies, VPZ was shown to reduce oral clearance and prolong the time to peak concentration of midazolam, indicating delayed metabolism and prolonged exposure[31]. In summary, VPZ offers potent acid suppression and improved efficacy in H. pylori treatment, even in cases of clarithromycin resistance, but attention to drug-drug interactions remains important.

The Maastricht VI/Florence consensus report suggests that VPZ-antibiotic combination therapy may improve eradication rates in antibiotic-resistant patients[32]. The prevalence of H. pylori infection varies significantly across countries and regions, with notable differences also observed in patterns of antibiotic resistance[33]. A multiregional prospective study in China reported on H. pylori drug resistance between 2010 and 2016, in which metronidazole and clarithromycin resistances have been as high as 78.2% and 22.1%, respectively[34]. Improving eradication rates in the face of increasing antibiotic resistance has become a focus of current research. A Japanese meta-analysis reported that the efficacy of VPZ was superior to PPI therapy in the treatment of clarithromycin-resistant patients[35]. Tanabe et al[36] conducted a clarithromycin drug sensitivity test in 212 patients and reported the same rate of clarithromycin resistance (23.5%) as China, and they compared the efficacy of VPZ triple therapy with that of PPIs, which was guided by drug sensitivity. They concluded that experienced VPZ triple therapy remains desirable, even in areas with high rates of clarithromycin resistance. Two studies conducted in Japan and Europe have confirmed that VPZ triple therapy was highly effective and well tolerated regardless of clarithromycin susceptibility[37,38]. Therefore, the use of a VPZ-based triple regimen may be a better option than PPI when clarithromycin drug sensitivity results are not available, and a recent study confirms this view[17]. Although international guidelines provide recommendations for H. pylori treatment, achieving consistent and satisfactory eradication rates remains challenging due to regional differences in disease patterns, antibiotic resistance, and drug availability. As such, performing antibiotic susceptibility testing prior to treatment remains a feasible and potentially valuable approach. In our study, patients with active gastrointestinal bleeding and other serious conditions were excluded, introducing a degree of selection bias. We advocate for broader inclusion criteria in future trials to better assess long-term efficacy and guide post-eradication monitoring strategies. Of the 48 patients excluded due to loss to follow-up or other reasons, stricter adherence monitoring should be implemented in future studies to reduce dropout rates. While our results confirmed the noninferiority of the 10-day VACa regimen, the slightly higher eradication rate observed with the 14-day regimen (93.9% vs 90.6% per protocol) may still influence clinical decisions. For high-risk patients, such as those with peptic ulcers or a family history of gastric cancer, clinicians may prefer the 14-day course despite similar statistical outcomes. The absence of increased adverse events in the VPZ group supports its practical use, with shorter regimens potentially enhancing patient adherence.

This study had several limitations. First, it assessed the efficacy and safety of VPZ only for initial H. pylori eradication; therefore, extended follow-up is necessary in future trials to evaluate long-term efficacy and guide post-eradication surveillance. Second, antibiotic susceptibility testing was not conducted, limiting the ability to tailor therapy in the context of regional resistance patterns. Future studies should incorporate susceptibility testing to optimize patient selection and treatment duration, particularly in areas with high resistance rates. Additionally, large-scale, multicenter trials across diverse regions of China are needed to confirm the efficacy of VPZ and to establish the most effective treatment regimens.

CONCLUSION

Triple therapy based on VPZ has a reasonable eradication rate, demonstrating noninferiority and safety in the initial eradication of H. pylori, indicating that VPZ can serve as an alternative to the first-line treatment method of eradicating H. pylori. There was no significant difference in eradication rates was observed between the 10-day and 14-day VAC regimens. Most consensus suggests that only regimens that reliably produce eradication rates ≥ 90% in this population should be used for empirical treatment. Therefore, conducting more clinical trials is necessary to optimize treatment regimens reduce the clinical drug burden, improve attention to adherence, and reduce the development of antibiotic resistance.

ACKNOWLEDGEMENTS

We would like to express our gratitude to all multicenter the hospital for recruiting to the clinical data of the patients.