Comparison of vonoprazan-based dual therapy with vonoprazan-based bismuth quadruple therapy for treatment-naive patients with Helicobacter pylori infection: A propensity score matching analysis

Abstract

Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to its robust acid-suppressing capacity. This study aimed to compare the efficacy of vonoprazan-based dual therapy (vonoprazan–amoxicillin, VA) with vonoprazan-based bismuth quadruple therapy (VBQT) as a first-line treatment for H pylori infection. This retrospective single-center non-inferiority study was conducted in China. Treatment-naive H pylori-positive patients aged 18 to 80 received one of the 2 treatment regimens at our center. The VA group received vonoprazan 20 mg twice daily and amoxicillin 1000 mg 3 times daily for 14 days, whereas the VBQT group received vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. The eradication rate was evaluated 4 to 6 weeks after treatment using the carbon-13/14 urea breath test. Propensity score matching was used to analyze eradication rates, adverse events (AEs), and patient compliance between the 2 groups. Initially, 501 patients were included, and after propensity score analysis, 156 patients were selected for the study. Intention-to-treat analysis showed eradication rates of 87.2% (95% CI, 79.8–94.6%) for the VA group and 79.5% (95% CI, 70.5–88.4%) for the VBQT group (P = .195). Per-protocol analysis demonstrated rates of 94.4% (95% CI, 89.2–99.7%) for the VA group and 96.8% (95% CI, 92.4–100%) for the VBQT group (P = .507). Non-inferiority was confirmed between the 2 groups, with P values < .025. The VA group showed a lower rate of AEs (10.3% vs 17.9%, P = .250) compared to the VBQT group. There were no significant differences in patient compliance between the 2 groups. In treatment-naive patients with H pylori infection, both the 14-day VA and VBQT regimens demonstrated comparable efficacy, with excellent eradication rates. Moreover, due to reduced antibiotic usage, lower rate of AEs, and lower costs, VA dual therapy should be prioritized.

1. Introduction

Helicobacter pylori infection is a highly prevalent chronic infection that affects almost half of the world’s population.^[1] The pooled prevalence of H pylori in Mainland China was 44.2%, with an estimated 589 million individuals infected.^[2] H pylori infection is strongly associated with chronic gastritis, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Studies have demonstrated that eradicating H pylori can prevent the development of chronic gastritis, lessen the recurrence of peptic ulcers, and reduce the risk of gastric cancer.^[3,4] According to current international guidelines, it is recommended to treat all individuals with H pylori infection, unless there are contraindications for treatment.^[5,6] Consequently, the effective eradication of H pylori remains a significant challenge for clinicians.

Most international guidelines for H pylori recommend 14-day bismuth-containing quadruple therapy (BQT) as the primary first-line treatment, consisting of proton-pump inhibitors (PPIs).^[3,5,6] The BQT regimen consists of a PPI, bismuth salts, and 2 antibiotics. Nevertheless, the eradication rate of the BQT regimen has progressively decreased, ranging from 79.5% to 86.6%, due to antibiotic resistance and inadequate acid suppression.^[7–9] In China, the primary resistance rates of H pylori to clarithromycin and amoxicillin are 37.00% and 2.20%, respectively.^[10]

Inhibition of gastric acid secretion plays a crucial role in H pylori.^[7] It promotes H pylori replication and enhances the bactericidal effects of pH-dependent antibiotics such as amoxicillin (AMO). Furthermore, the occurrence of H pylori resistance to AMO remains rare in China.^[10,11] The latest Chinese management guidelines for H pylori recommend the use of high-dose dual therapy (HDDT) as a first-line and second-line eradication treatment for H pylori.^[5] This regimen includes high-dose AMO (≥3.0 g/d) and double-dose PPI. Its objective is to enhance the eradication rate of H pylori and minimize adverse events (AEs) by reducing the number of drugs, increasing the dosage, and frequency of administration. Generally, the HDDT regimen demonstrates an eradication rate comparable to that of PPI-based BQT (PBQT), and several studies have indicated a lower occurrence of AEs and lower costs.^[5,12–15] Nevertheless, both regimens fail to meet the international consensus of achieving a 90% eradication rate, underscoring the necessity for further optimization of treatment strategies to enhance H pylori eradication rates.

Vonoprazan (VPZ) is a novel class of acid suppressants known as potassium-competitive acid blockers, with the distinction of being the first of its kind.^[16] In comparison to PPIs, VPZ demonstrates superior and sustained acid suppression. In a study involving healthy volunteers, the plasma concentration–time profiles of VPZ revealed rapid absorption, with a median T_max of ≤2 hours and a mean elimination half-life of up to 9 hours, indicating dose-dependent acid suppression. By the seventh day of administration, the mean 24-hour intragastric pH > 4 holding time ratio with a 40 mg dose of VPZ was 100%, and similarly, the mean nighttime pH > 4 holding time ratio was 100%.^[17]

Hence, substituting PPIs with VPZ for the treatment of H pylori infection has the potential to yield improved outcomes. Initially introduced in Japan, VPZ has been extensively studied and has consistently shown a substantial enhancement in the eradication rate of triple therapy for H pylori without increasing the incidence of AEs.^[18–20]

Chinese researchers have conducted several studies on the substitution of VPZ for PPIs in BQT and dual therapy. The results consistently indicate that VPZ-based BQT (VBQT) achieves higher or non-inferior eradication rates than the PBQT regimen.^[21–23] The VBQT regimen achieved eradication rates ranging from 91.5% to 97.5% (per-protocol analysis), surpassing the threshold of 90% for satisfactory outcomes. Additionally, a 14-day VPZ-based dual therapy (vonoprazan–amoxicillin, VA) demonstrated significantly superior or non-inferior efficacy compared to PBQT regimen, with a notably lower occurrence of AEs.^[24–27] The VA regimen consistently achieved satisfactory eradication rates ranging from 95.6% to 98.5% (per-protocol analysis), surpassing the threshold of 90% for satisfactory outcomes.

Several studies have demonstrated satisfactory eradication efficacy of VA and VBQT regimens compared to standard PBQT. However, no studies have compared the efficacy of VA and VBQT regimens in eradicating H pylori. Theoretically, the 14-day VA regimen can achieve non-inferior eradication efficacy compared to the 14-day VBQT regimen as a first-line treatment for H pylori. To further validate this hypothesis and explore improved H pylori eradication strategies, we conducted a controlled trial.

In this study, we compared the efficacy and safety of VA and VBQT regimens as first-line treatment options for eradicating H pylori in a propensity score-matched (PSM) cohort, with the aim of providing an evidence-based reference for clinical practice.

2. Materials and methods

2.1. Study design and ethics

This was a single-center, retrospective, non-inferiority, controlled study conducted in accordance with the ethical guidelines of the Helsinki Declaration. This study was approved by the Ethics Committee of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University (Ethics Committee Approval Number: 2023-081). The study was registered at ClinicalTrials.gov (Registration Number ChiCTR2300077541). Patients who received the VA regimen were predominantly enrolled in a clinical randomized controlled trial registered with the Chinese Clinical Trial Registry (www.chictr.org.cn; Registration Number ChiCTR2300070239). In this study, patients in the VA dual therapy regimen take a dosage of 1g of amoxicillin 3 times a day. Written informed consent was obtained from all the participants in this group. The objective of this study was to compare the efficacy of 14-day VA dual therapy with 3 different AMO doses as a first-line treatment for H pylori infection in a randomized controlled manner. The VBQT regimen utilizes existing human data, obviating the need for additional participant recruitment and waiting for informed consent.

2.2. Study population

We collected patient data from the Digestive Endoscopy Center at the Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University in Jinan, China, and reviewed the medical records of individuals who underwent H pylori eradication therapy from January 1, 2022, to October 30, 2023.

Inclusion criteria: Patients aged 18 to 80 years who were diagnosed with H pylori infection through at least one of the following methods were eligible for the clinical study: carbon-13/14 urea breath test (¹³C/¹⁴C-UBT), H pylori antibody detection, pathological examination, and first-line eradication therapy with VA or VBQT regimens.

Exclusion criteria were as follows: Patients receiving salvage therapy; patients who received PPI, potassium-competitive acid blockers, bismuth, or antibiotic therapy within the past 4 weeks; patients who had undergone gastric resection; patients who were pregnant, breastfeeding, or allergic to the study drugs; patients with severe cardiovascular, respiratory, endocrine, renal, hepatic, or hematological diseases; patients with severe neurological or psychiatric disorders; and patients with incomplete follow-up.

2.3. Treatment and follow-up

The VA regimen comprised VPZ (Takeda Pharmaceutical Co., Ltd., Tianjin, China) 20 mg, administered twice daily before meals, and AMO (United Laboratories Co., Ltd., Zhuhai, China) 1000 mg, administered 3 times daily immediately after meals, for a period of 14 days. The VBQT regimen included VPZ (Takeda Pharmaceutical Co., Ltd.) 20 mg, AMO (United Laboratories Co., Ltd.) 1000 mg, clarithromycin (Guangdong Dongyang Pharmaceutical Co., Ltd., Guangdong Province, China) 500 mg, and bismuth potassium citrate (Livzon Pharmaceutical Group Inc., Zhuhai, China) 220 mg. VPZ and bismuth were taken 30 minutes before meals, while AMO and clarithromycin were taken immediately after meals, both twice daily for 14 days.

Demographic data, including name, sex, age, body mass index (BMI), smoking history, alcohol consumption history, comorbidities (such as hypertension, coronary heart disease, diabetes, cerebrovascular disease, and thyroid disease), and endoscopy findings, were obtained by reviewing medical records and conducting telephone interviews.

Each participant was required to record any AEs during the treatment and their compliance with the regimen. We performed follow-up telephone interviews with patients within 1 month of completing their medication to determine the occurrence of AEs and assess patient compliance. At least 4 weeks after completion of the treatment, the H pylori infection status was assessed using the ¹³C/¹⁴C-UBT.

2.4. Propensity score matching

PSM was employed to balance the factors including age, sex, patient type, BMI, smoking history, alcohol consumption history, number of chronic diseases, and endoscopy findings to minimize potential confounding and selection bias. Binary logistic regression was used to perform PSM in a 1:1 ratio, yielding propensity scores for each participant with a caliper value set at 0.1. R statisitcs software 4.0.1 was used for participant selection in the PSM analysis, for both the target patients and control patients.

2.5. Data processing and research results

The primary endpoint of this study was the eradication rate of H pylori. The ¹³C/¹⁴C-UBT results were used to assess eradication success or failure. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed. All patients enrolled in the study will be included in the ITT analysis, while patients who did not undergo the ¹³C/¹⁴C-UBT follow-up test will be categorized as treatment failures. Patients who achieved >80% drug compliance and underwent ¹³C/¹⁴C-UBT were included in PP analysis.

The secondary endpoints were the incidence and severity of AEs and patient compliance. The severity of the AEs was classified as mild, moderate, or severe. Mild referred to adverse symptoms that did not require treatment, moderate referred to adverse symptoms that could be controlled with treatment but did not require hospitalization, and severe referred to patients with adverse symptoms who required hospitalization or experienced study-related death. Poor compliance was defined as taking less than 80% of the prescribed medications.

2.6. Sample size calculation and statistical analysis

Sample size calculation for a 2-sample non-inferiority study was performed using the PASS 11 software (NCSS, LLC, Kaysville, UT). The VBQT regimen has been reported to achieve H pylori eradication rates ranging from 91.5% to 97.5%.^[21–23] The VA regimen (VPZ 20 mg twice daily + AMO 1000 mg 3 times) showed an eradication rate of 95.9%.^[26] In our study, we assumed that both VA and VBQT regimens would have an eradication rate of 95%. Assuming power, alpha, and non-inferiority margins of 0.80, 0.025, and −0.10, respectively, we calculated a sample size of 150 patients (75 patients in each group) to confirm the non-inferiority of the VA regimen to the VBQT regimen.

Quantitative data were presented as mean ± standard deviation (SD) and compared using Student t test. Categorical data were described by absolute numbers and percentage frequencies and compared using chi-square and Fisher’s exact tests. Statistical significance was set at a 2-tailed P value < .05.

Stepwise logistic regression was conducted for multivariate analysis to identify the independent factors affecting the eradication rate, with a P value < .2 in the univariate analysis. SAS 9.4 software (SAS Institute, Cary, NC) was used for non-inferiority analysis, whereas all other analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 24.0 (IBM Corporation, Armonk, NY).

3. Results

3.1. Patient enrollment and baseline characteristics

As shown in Figure 1, a total of 549 patients were evaluated in this study, of which 48 were excluded due to noncompliance with inclusion criteria (n = 8), loss to follow-up (n = 18), or not taking medication (n = 22). Among the 501 patients, 81 were assigned to the VA group and 420 were assigned to the VBQT group. The clinical characteristics of these patients are summarized in Table 1. Based on the PSM results, 3 and 342 patients were respectively excluded from the VA and VBQT groups, resulting in 78 patients in each group for analysis. In the VA group, 6 patients did not undergo ¹³C/¹⁴C-UBT, and among them, 3 patients took less than 80% of the prescribed medications. In the VBQT group, 13 patients refused the ¹³C/¹⁴C-UBT, and 3 patients took <80% of the medications. Therefore, 72 patients in the VA group and 62 patients in the VBQT group were included in the PP analysis. After PSM, no statistically significant differences were observed in the demographic and clinical characteristics between the 2 treatment groups (Table 2).

Figure 1.

Flow chart of patient enrollment. ITT = intention-to-treat, PP = per protocol, VA = vonoprazan–amoxicillin dual therapy, VBQT = vonoprazan-based bismuth-containing quadruple therapy.

Table 1.

Baseline demographics of study subjects before PSM.

Characteristics	VA (N = 81), n (%)	VBQT (N = 420), n (%)	P value
Gender
Male	40 (49.4)	167 (39.8)	.107
Female	41 (50.6)	253 (60.2)
Age (years, mean ± SD)	43.00 ± 11.80	44.18 ± 13.40	.423
Patient type
Outpatient	51 (63.0)	335 (79.8)	.001
Inpatient	30 (37.0)	85 (20.2)
BMI (kg/m2, mean ± SD)	23.67 ± 3.12	24.04 ± 3.18	.327
Smoking	17 (21.0)	60 (14.3)	.126
Alcohol drinking	25 (30.9)	113 (26.9)	.465
Number of comorbidities
0	68 (84.0)	345 (82.1)	.479
1	12 (14.8)	51 (12.1)
2	1 (1.2)	19 (4.5)
More than 2	0 (0.0)	5 (1.2)
Endoscopic findings
No gastroscopy	26 (32.1)	172 (41.0)	.080
Only non-atrophic gastritis	25 (30.9)	112 (26.7)
Only atrophic gastritis	24 (29.6)	68 (16.2)
Mainly Gastritis and esophagitis	2 (2.5)	18 (4.3)
Mainly gastritis and gastric ulcer and/or duodenal ulcer	4 (4.9)	24 (5.7)
Mainly gastritis and globoduodenitis	0 (0.0)	9 (2.1)
Mainly gastritis and cardiac polyp and/or gastric polyp	0 (0.0)	12 (2.9)
Other complex diagnosis	0 (0.0)	5 (1.2)

Student t test, Chi-square and Fisher’s exact tests was used for statistical analysis. All results were considered significant if the P value was < .05.

BMI = body mass index, PSM = propensity score matching, SD = standard deviation, VA = vonoprazan-amoxicillin dual therapy, VBQT = vonoprazan-based bismuth-containing quadruple therapy.

Table 2.

Baseline demographics of study subjects after PSM.

Characteristics	VA (N = 78), n (%)	VBQT (N = 78), n (%)	P value
Gender
Male	37 (47.4)	39 (50.0)	.749
Female	41 (52.6)	39 (50.0)
Age (years, mean ± SD)	42.38 ± 11.34	44.05 ± 13.44	.404
Patient type
Outpatient	51 (65.4)	50 (64.1)	.867
Inpatient	27 (34.6)	28 (35.9)
BMI	23.83 ± 2.99	23.96 ± 2.99	.794
Smoking	15 (19.2)	11 (14.1)	.390
Alcohol drinking	23 (29.5)	25 (32.1)	.729
Number of comorbidities
0	66 (84.6)	65 (83.3)	1.000
1	11 (14.1)	11 (14.1)
2	1 (1.3)	2 (2.6)
Endoscopic findings
No gastroscopy	26 (33.3)	33 (42.3)	.639
Only non-atrophic gastritis	24 (30.8)	17 (21.8)
Only atrophic gastritis	22 (28.2)	20 (25.6)
Mainly gastritis and esophagitis	2 (2.6)	2 (2.6)
Mainly gastritis and gastric ulcer and/or duodenal ulcer	4 (5.1)	6 (7.7)

Student t test, Chi-square and Fisher’s exact tests was used for statistical analysis. All results were considered significant if the P value was < .05.

BMI = body mass index, PSM = propensity score matching, SD = standard deviation, VA = vonoprazan-amoxicillin dual therapy, VBQT = Vonoprazan-based bismuth-containing quadruple therapy.

3.2. Efficacy

The efficacy of H pylori eradication is presented in Table 3. As per the ITT analysis, the eradication rates for H pylori in the VA and VBQT groups were 87.2% (95% CI, 79.8–94.6%) and 79.5% (95% CI, 70.5–88.4%), respectively, exhibiting a marginal difference of 7.7% (95% CI, −3.9 to 19.3%) between the groups. In the PP analysis, the H pylori eradication rates in the VA and VBQT were 94.4% (95% CI, 89.2–99.7%) and 96.8% (95% CI, 92.4–100%), respectively, with a marginal difference of −2.3% (95% CI, −9.2 to 4.6%) between the groups. Thus, no statistically significant disparities were observed in H pylori eradication rates between the VA and VBQT regimens (P > .05 in both ITT and PP analyses). In both the ITT and PP analyses, the adjusted 95% confidence interval for the difference exceeded the predetermined non-inferiority margin of −0.1. Crucially, the non-inferiority of the VA regimen relative to the VBQT regimen was firmly established (P < .025 in both the ITT and PP analyses).

Table 3.

Eradication rates of each therapy group.

	VA (n = 78)	VBQT (n = 78)	Adjusted 95% CI for difference	P value for noninferiority†	P value for difference*
ITT	87.2% (68/78)	79.5% (62/78)	7.7%	.001	.195
95% CI	79.8% to 94.6%	70.5% to 88.4%	−3.9% to 19.3%
PP	94.4% (68/72)	96.8% (60/62)	−2.3%	.014	.507
95% CI	89.2% to 99.7%	92.4% to 100%	−9.2% to 4.6%

CI = confidence interval, ITT = intention-to-treat, PP = per protocol, VA = vonoprazan–amoxicillin dual therapy, VBQT = vonoprazan-based bismuth-containing quadruple therapy.

^*The P values were obtained from 2-sided comparisons of differences between the VA and VBQT groups. All results were considered significant if the P value was < .05.

^†The P values were obtained from 1-sided test comparisons of non-inferiority between the VA and VBQT groups. All results were considered significant if the P value was <.025.

3.3. AEs, patient compliance, and costs

Eight patients in the VA group experienced adverse events. One patient discontinued the study medication owing to AEs. Fourteen patients in the VBQT group experienced AEs, with 1 patient having a moderate AE. Two patients discontinued the study medication due to AEs. Common AEs included abdominal bloating, diarrhea, abdominal discomfort, nausea, skin rash, bitter mouth, anorexia, and itching (Table 4). Most AEs were mild and resolved gradually after treatment completion. There were no severe AEs during the study period. The occurrence of AEs in the Group VA was lower than that in the Group VBQT; however, the disparity was not statistically significant (10.3% vs 17.9%, P = .250). The compliance rate among patients in both groups was 96.2% (P = 1.000). Medication costs were calculated and compared between the 2 treatment regimens. The cost of VA treatment was 348.6 yuan, which was lower than that of VBQT treatment (532.7 yuan).

Table 4.

The adverse events, patient compliance and costs of each therapy group.

	VA (n = 78), % (n/N)	VBQT (n = 78), % (n/N)	P value
No. of patients with adverse event	10.3 (8/78)	17.9 (14/78)	.250
Diarrhoea	6.4 (5/78)	5.1 (4/78)	1.000
Abdominal bloating	1.3 (1/78)	1.3 (1/78)	1.000
Nausea	2.6 (2/78)	2.6 (2/78)	1.000
Abdominal discomfort	0 (0/78)	1.3 (1/78)	1.000
Skin rash	0 (0/78)	1.3 (1/78)	1.000
Bitter mouth	0 (0/78)	2.6 (2/78)	.497
Anorexia	0 (0/78)	1.3 (1/78)	1.000
Itching	0 (0/78)	1.3 (1/78)	1.000
Giddy	0 (0/78)	1.3 (1/78)	1.000
Total no. of adverse events	8	14
Mild	8	13
Moderate	0	1
Severe	0	0
Compliance	96.2 (75/78)	96.2 (75/78)	1.000
Costs (yuan)	348.6	532.7

Chi-square and Fisher’s exact tests was used for statistical analysis. All results were considered significant if the P value was < .05.

VA = vonoprazan–amoxicillin dual therapy, VBQT = vonoprazan-based bismuth-containing quadruple therapy.

3.4. Factor analysis

Univariate analysis was conducted to investigate potential factors affecting H pylori eradication efficacy, including sex, age, patient type, BMI, smoking history, alcohol consumption, number of comorbidities, endoscopic findings, AEs, severity of AEs, and compliance. Good compliance, female, inpatient status, alcohol drinking and VBQT regimen were identified as potential influencing factors in the analysis. In the final multivariate analysis, good compliance was the only confirmed beneficial factor for eradication success (Table 5).

Table 5.

Factors affecting Helicobacter pylori eradication efficacy.

	Eradication success (N = 130), n (%)	P value
Gender
Female	59 (45.4)	.061
Fale	71 (54.6)
Age, year	43.02 ± 12.84	.661
Patient type
Inpatient	88 (67.7)	.090
Outpatient	42 (32.3)
Endoscopic findings
No gastroscopy	50 (38.5)	.820
Only non-atrophic gastritis	34 (26.1)
Only atrophic gastritis	36 (27.7)
Mainly gastritis and esophagitis	3 (2.3)
Mainly gastritis and gastric ulcer and/or duodenal ulcer	7 (5.4)
Compliance
No	2 (1.5)	.005
Yes	128 (98.5)
Number of comorbidities
0	109 (83.8)	.723
1	19 (14.6)
2	2 (1.6)
BMI	23.84 ± 2.94	.613
Smoking
No	110 (84.6)	.354
Yes	20 (15.4)
Alcohol drinking
No	94 (72.3)	.070
Yes	36 (27.7)
AEs
No	113 (86.9)	.427
Yes	17(13.1)
Severity of AEs
No	113 (86.9)	.560
Mild	16 (12.3)
Moderate	1 (0.8)
Treatment therapies
VA	68 (52.3)	.196
VBQT	62 (47.7)
Multivariate analyses (adjusted OR [95% CI])
Gender
Male	Reference	.511
Female	1.483 (0.458, 4.797)
Patient type
Outpatient	Reference	.130
Inpatient	0.471 (0.178, 1.248)
Compliance
No	Reference	.005
Yes	14.640 (2.283, 93.879)
Alcohol drinking
No	Reference	.438
Yes	0.650 (0.218, 1.933)
Treatment therapies
VA	Reference	.194
VBQT	0.544 (0.217, 1.363)

Stepwise logistic regression was used for statistical analysis. P value < 0.05 was considered significant.

AE = adverse event, CI = confidence interval, VA = vonoprazan–amoxicillin dual therapy, VBQT = vonoprazan-based bismuth-containing quadruple therapy.

4. Discussions

This was a retrospective controlled study evaluating the efficacy and safety of VA versus VBQT regimens for eradicating H pylori infection. In this study, we employed PSM and found that the eradication rate of VA regimen was non-inferior to that of VBQT regimen (94.4% vs 96.8%, PP analysis), exceeding the recommended standard of 90% as per guidelines. Additionally, the VA regimen exhibited a lower incidence of AEs and lower costs than VBQT. No severe AEs were observed in either group. Both regimens exhibited good patient compliance, which was comparable between them, and good patient compliance was identified as a crucial factor contributing to treatment success.

In China, PBQT regimen is recommended as the primary empirical treatment for H pylori eradication. However, the eradication rate has been declining, primarily because of rising antibiotic resistance or inadequate acid suppression.^[7,8] Compared to PPI, VPZ has several advantages in the treatment of H pylori infection. It has a longer-lasting acid-suppressing effect, leading to an extended period of neutral pH in the stomach,^[28–30] promoting H pylori replication and enhancing the bactericidal activity of antibiotics dependent on bacterial growth.^[31] Furthermore, VPZ has the potential to enhance the concentration and stability of AMO and clarithromycin in the gastric mucosa.^[32] Additionally, VPZ exhibits faster onset of action than PPI, maintaining optimal pH for H pylori treatment throughout the entire course after the initial dose.^[33,34] VPZ’s pharmacokinetic characteristics are not affected by CYP2C19 polymorphism, resulting in reduced interindividual variation in H pylori eradication. Numerous studies have indicated that 7-day triple therapy with VPZ is significantly more effective than that with PPI.^[35] An increasing number of Chinese researchers have adopted VPZ as a substitute for PPIs in BQT to enhance the eradication rates of H pylori. Several studies have demonstrated the superiority or at least non-inferiority of the VBQT regimen compared to the PBQT regimen.^[21–23] The VBQT regimen has consistently demonstrated an excellent eradication rate, with eradication rates ranging from 94.1% to 97.5% (PP analysis),^[21,23] consistent with the eradication rate of the VBQT regimen in this study.

In recent years, 14-day HDDT has shown satisfactory bactericidal effects, with commonly used regimens such as AMO 750 mg + esomeprazole 20 mg 4 times daily.^[5] The eradication rates of HDDT range from 88% to 95% in the initial or rescue treatment of H pylori, with a meta-analysis showing similar eradication rates compared to the currently recommended first-line regimens.^[36] Additionally, HDDT is associated with lower rates of AEs and costs.^[37] The satisfactory efficacy of the HDDT can be attributed to several factors. Firstly, the high dose and frequency of PPIs help maintain a near-neutral gastric pH, increasing the sensitivity of H pylori to AMO. Secondly, rare instances of AMO resistance have been observed in the Chinese population.^[10,11] Finally, AMO, a pH-dependent and time-dependent antibiotic, shows increased benefits from higher dosing frequency and dosage, leading to elevated blood drug concentrations.^[15]

A Japanese study published in Gut in 2020 demonstrated that a 7-day VA regimen (VPZ 20 mg + AMO 750 mg twice daily) achieved an H pylori eradication rate of 85%.^[38] Based on this finding, Chinese researchers have been exploring the applicability of VA dual therapy in the Chinese population. However, short-term or low-frequency administration of the VA regimen may not be suitable for the Chinese population. For instance, a study conducted by Lanzhou University reported an eradication rate of only 63.5% for the VA regimen (VPZ 20 mg twice daily + AMO 750 mg 4 times daily for 7 days).^[39] Similarly, in a study by Nanchang University, a high-dose VA regimen (VPZ 20 mg twice daily + AMO 1000 mg 3 times daily) for 10 days showed an eradication rate of 81.1%, and a low-dose VA regimen (VPZ 20 mg twice daily + AMO 1000 mg twice daily) for 10 days showed an eradication rate of 89.2%, both of which did not achieve satisfactory eradication rates (>90%).^[40] Consistent with our results, VA regimens that have achieved satisfactory eradication rates in current research are typically administered for 10 to 14 days, with AMO dosages ≥ 3.0g/day, and administered 3 or 4 times daily.^[24–26,41] A recent retrospective cohort study demonstrated that a 14-day VA regimen (VPZ 20 mg twice daily + AMO 1000 mg 3 times daily) had comparable efficacy (94.1% vs 92.8%) and safety to a 14-day PPI-based dual therapy regimen (AMO 1000 mg 3 times daily + esomeprazole 20 mg 4 times daily),^[42] These findings indicated that the acid suppression strength of VPZ at 40 mg daily is equivalent to 4 times the standard dose of PPI, with a lower dosing frequency and improved convenience for patients. However, studies conducted in the United States and Europe have shown unacceptable eradication rates (<80%) for the 14-day VA regimen, which may be attributed to racial differences and higher BMI, leading to inadequate gastric acid suppression.^[43]

The 14-day BQT regimen has several shortcomings, including high cost, potential for bacterial resistance due to the long-term use of multiple antibiotics, imbalanced gut microbiota, poor patient compliance, and increased AEs.^[44] Thus, the VA regimen may offer a solution to these issues. Although there have been conflicting reports on the safety of VPZ-containing regimens, overall, VPZ appears to be safe. Previous studies have documented adverse event (AE) rates ranging from 11% to 39.2% for the VA regimen^{[24–26,40,45]} and from 15% to 30.0% for the VBQT regimen.^[21,23] Our study revealed a lower incidence of AEs in the VA group than in the VBQT group, although the difference was not statistically significant. Furthermore, the incidence of AEs was lower than that reported in previous studies, with no severe AEs. This may be attributed to the regular follow-up and good communication with patients in our study, resulting in a relatively low incidence of AEs. Furthermore, a study conducted by Hu et al^[26] revealed that the VA regimen had a lesser impact on the gut microbiota of patients compared to the PBQT regimen. Additional research is required to explore the effects of the VBQT regimen on the gut microbiota.

Good patient compliance significantly contributes to treatment success. Enhanced education and investigator follow-up have been linked to improved compliance and a positive impact on H pylori eradication.^[46,47] A meta-analysis has shown that technology-enhanced communication strategies can effectively improve compliance and increase the eradication rate.^[48] In our study, all patients received comprehensive oral and written medical instructions, resulting in a high compliance rate of 96.2% among patients, consistent with previous research findings.^[21]

In our study, more than 20% of the cases in the VBQT group were not included in the PP analysis, however, we separately utilized both ITT analysis and PP analysis to assess the bactericidal efficacy of the 2 regimens. The consistent conclusions drawn from both analyses further enhance the credibility of the research results.

However, our study had several limitations. First, this was a single-center retrospective controlled study. Nevertheless, we used propensity score matching to minimize bias. In the future, it will be necessary to conduct multicenter, large-sample, prospective randomized controlled trials to further validate our findings. Second, we did not test for H pylori antibiotic resistance. Nevertheless, both groups achieved favorable eradication rates. Nonetheless, antimicrobial susceptibility testing is time consuming, unstable, and expensive. Finally, the participants were exclusively Chinese. Further research is needed to ascertain the efficacy of the VA and VBQT regimens in other ethnic populations.

5. Conclusion

The eradication rates of the VA and VBQT regimens are comparable, and both demonstrate excellent efficacy. Both regimens exhibit similar patient compliance and can be regarded as first-line treatment options for H pylori infection. However, it is important to note that the VA regimen entails reduced antibiotic usage, lower incidence of AEs and costs than the VBQT regimen. Therefore, the VA regimen should be prioritized and recommended.

Acknowledgments

I would like to express my gratitude to the Paperpal system for their assistance in correcting the grammar in the article. I also want to thank Professor Zhang Jie for the support with data statistics.

Author contributions

Conceptualization: Zhu Liu, Xin Chen, Dong-Jie Sun.

Data curation: Wen-Wen Zhao.

Formal analysis: Luan Kou.

Methodology: Zhu Liu, Dong-Jie Sun.

Project administration: Feng-Yu Gao.

Writing – original draft: Wen-Wen Zheng, Jiao-Rong Hao.