Due to the increasing prevalence of antimicrobial resistance, the efficacy of standard triple therapy for Helicobacter pylori (H. pylori) infection has declined, with eradication rates now falling below 80% in most countries. Although bismuth quadruple therapy and concomitant therapy are advised in regions with high clarithromycin resistance, these treatments commonly cause frequent adverse events and require the use of two or three antibiotics. This review article evaluates the effectiveness of 14-day mono-antibiotic therapies for H. pylori infection through randomized controlled trials conducted from 1 October 2014 to 1 October 2024. The pooled eradication rates for 14-day high-dose amoxicillin/proton pump inhibitor (PPI) dual therapies were 86.1% (3335/3875; 95% confidence interval (CI): 85.1-87.2%) by intention-to-treat (ITT) analysis and 87.3% (3232/3702; 95% CI: 86.2-88.4%) by per-protocol (PP) analysis. For 14-day high-dose amoxicillin/vonoprazan dual therapies, the rates were 87.4% (1085/1241; 95% CI: 85.5-89.2%) by ITT and 93.0% (1044/1124; 95% CI: 91.5-94.5%) by PP. In the penicillin-allergic population, 14-day tetracycline/vonoprazan dual therapy showed eradication rates of 92.0% (138/150) by ITT and 95.1% (135/142) by PP. In conclusion, 14-day tetracycline/vonoprazan dual therapy presents an effective option for eradicating H. pylori in patients allergic to penicillin. For those without a penicillin allergy, first-line treatments can include 14-day mono-antibiotic regimens, such as high-dose amoxicillin/PPI dual, high-dose amoxicillin/vonoprazan dual, and tetracycline/vonoprazan dual therapies.

The efficacy of the 14-day esomeprazole-amoxicillin (EA) dual therapy in eradicating Helicobacter pylori (H. pylori) has been widely discussed previously. Vonoprazan, a novel potassium-competitive acid blocker, presents rapid, potent, and long-lasting acid inhibitory effects compared to esomeprazole. However, there is currently a scarcity of direct comparisons between the 10-day vonoprazan-amoxicillin (VA) and the 14-day EA dual therapy for H. pylori eradication.

This study aimed to compare the efficacy and safety of the 10-day VA and the 14-day EA dual therapy for H. pylori first-line eradication.

This study was a prospective, multicenter, open-label, randomized controlled trial.

The study was conducted at 10 hospitals in China. In total, 570 newly diagnosed H. pylori-infected patients were recruited from April 2023 to February 2024. These patients were randomly assigned to either the 10-day VA group (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily) or the 14-day EA group (esomeprazole 20 mg four times daily + amoxicillin 750 mg four times daily). The primary outcome was the eradication rate, with secondary outcomes including adverse events and compliance.

The 10-day VA regimen outperformed the 14-day EA regimen in terms of eradication rates in intention-to-treat (ITT) analysis (85.4% vs 76.7%, p = 0.008), modified ITT analysis (90.7% vs 84.8%, p = 0.036), and per-protocol (PP) analysis (91.1% versus 85.5%, p = 0.047). The non-inferiority p-values in all three analyses were less than 0.001. No statistically significant difference was observed in the incidence of adverse events between the two groups (9.1% vs 11.7%, p = 0.308). The 10-day VA regimen demonstrated higher compliance compared to the 14-day EA regimen (p = 0.006).

The 10-day VA dual therapy showed a satisfactory eradication rate of 91.1% (PP analysis), demonstrating good safety and better compliance compared to the 14-day EA dual therapy as the first-line eradication.

This trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300070475) on April 12, 2023.

A new, sensitive, and rapid isocratic reversed phase chromatographic method (RP-HPLC-UV) was developed for simultaneous separation of two newly co-formulated antiulcer mixtures; Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)], and Amoxicillin, Lansoprazole and Clarithromycin [Mixture (II)]. Analytical separation was performed using a Promosil C18 column and ultraviolet detection at 210 nm. The separation was achieved within only 8 min. For both mixtures, an aqueous solution, composed of (Acetonitrile: Methanol: 0. 2 M phosphoric acid) within ratio of (30: 30: 40) adjusted to final pH 3.0, was the mobile phase. This method was validated as per the International Conference on Harmonization guidelines. The linearity ranges of these proposed method of the (Mixture (I)) were 25.0-400.0 µg/mL Amoxicillin, 0.5-8.0 µg/mL Vonoprazan, and 12.5-200.0 µg/mL Clarithromycin. And the linearity ranges of the (Mixture (II)) were 10.0-300.0 µg/mL Amoxicillin, 0.3-9.0 µg/mL Lansoprazole and 5.0-150.0 µg/mL Clarithromycin. This method was firstly applied for effective separation of Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)]. It fulfilled good repeatability, sensitivity, and accuracy (R.S.D. < 2.0%). The mean recoveries of the analytes in their Tri-Pak formulations were acceptable. The greenness of the developed chromatographic methods was assessed using an Eco-scale method and it was applied for content uniformity testing as per the United States Pharmacopoeia (USP) and the acceptance value of Amoxicillin, in Mixture (I) was 2.88, the acceptance values for Amoxicillin, Lansoprazole in Mixture (II) were 2.592, 2.424, respectively.

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.

To update evidence-based data comparing the efficacy and safety of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) in eradicating Helicobacter pylori infection through meta-analysis.

Multiple databases were systematically searched for randomized controlled trials (RCTs) published up to May 18, 2023. Dichotomous data were evaluated using risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis, sensitivity analysis, risk of bias assessment, and quality of evidence evaluation were performed.

Twenty RCTs containing 7891 subjects were included in the analysis. There was no statistically significant difference in H. pylori eradication rate between HDDT and BQT in the intention-to-treat (ITT) analysis (86.31% vs 84.88%; RR 1.02, 95% CI 1.00-1.04, P = 0.12). In the per-protocol (PP) analysis, the eradication rates for HDDT and BQT were 90.27% and 89.94%, respectively (RR 1.01, 95% CI 0.99-1.03, P = 0.44). Adverse events were significantly lower with HDDT than with BQT (RR 0.44, 95% CI 0.38-0.51, P < 0.00001). Patient adherence was significantly different between the two groups (RR 1.01, 95% CI 1.00-1.03, P = 0.02). Subgroup analysis based on antibiotic combinations within the BQT group showed a significantly higher eradication rate for HDDT than for BQT only when BQT used amoxicillin combined with clarithromycin (P = 0.0009).

HDDT showed comparable efficacy with BQT for H. pylori eradication, with fewer adverse effects and higher compliance. Due to regional differences, antibiotic resistance rates, and combined BQT antibiotics, more studies are needed for further validation and optimization of HDDT.

Current global variations exist in Helicobacter pylori (H. pylori) eradication regimens. Triple therapy (TT), bismuth quadruple therapy (BQT), and high-dose dual therapy (HDDT) currently represent the predominant regimens. These regimens diverge in terms of treatment duration, the utilization of susceptibility testing, acid-inhibiting drug administration, and patient education. We conducted a comprehensive systematic literature review on these H. pylori treatment regimens. Our review aims to provide standardized treatment recommendations for H. pylori, reducing the risk of amalgamating findings from diverse eradication regimens. Recent research suggests that the optimal treatment duration for TT and BQT may be 14 and 10 days, respectively. Selecting the appropriate treatment duration for HDDT should rely on regional research evidence, and 14 days may be the optimal duration. The incorporation of susceptibility testing in TT is of paramount importance. In the case of BQT, the absence of susceptibility testing may be considered as an option, contingent upon cost and availability, and should be determined based on local antibiotic resistance patterns and the efficacy of empirical regimens. The type and dosage of acid-inhibiting drug would affect the efficacy of these regimens. Acid-inhibiting drugs should be selected and applied reasonably according to the population and therapies. Adequate patient education plays a pivotal role in the eradication of H. pylori. In regions with accessible local research evidence, the 10-day empirical BQT regimen may be considered a preferred choice for H. pylori eradication.

Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is considered by most countries to have good eradication rates, while the 7- and 10-day studies have been more widely explored, however, we find that their results are different. The applicability of the shorter and less expensive 10-day neo-dual therapy to our country has not yet been confirmed.

The patients were divided into 3 groups of 200 each by randomization method. Group A: patients received vonoprazan 20 mg, bid + amoxicillin(1 g), tid, for 14 days. Group B: vonoprazan (20 mg) bid + amoxicillin (1 g) tid, duration of treatment is 10 days, group C: rabeprazole (20 mg) bid + bismuth potassium citrate tablets/tinidazole tablets/clarithromycin tablets, combined package (4.2 g), bid, duration of treatment 14 days. The main comparisons were H pylori eradication rate, adverse drug reaction profile and cost-effect ratio in each group.

The eradication rates of groups A, B, and C were 92.5%, 91.6%, and 80.1%, respectively. There was no significant difference in the eradication rates of groups A and B (P > .05), groups A and B had statistically significantly better eradication rates than group C (P < .05). The incidence of adverse reactions in groups A, B, and C was 9.5%, 8.5%, and 17.0%, respectively. There was no difference in the incidence of adverse reactions between A and B: (P > .05), The incidence of adverse reactions was statistically significantly lower in groups A and B than in group C (P < .05). Logistic regression analysis showed nonsmokers had a higher eradication rate (OR 2.587, 95% CI: 1.377-4.859, P = .003), and taller patients were more likely to have successful eradication (OR 1.052, 95% CI: 1.008-1.097, P = .020). Group B had the lowest cost-benefit analysis results.

Group B had an acceptable eradication rate, the lowest incidence of adverse effects, and the lowest cost analysis. Eradication is more likely to be successful in patients who do not smoke and in those who are taller.

Helicobacter pylori (H. pylori) infection is one of the most important public health issues, and bismuth-containing quadruple therapy (BQT) is the first-line therapeutic option. This study aimed to compare the efficacy and safety of high-dose dual therapy (HDDT) and BQT in eradicating H. pylori.

Randomized controlled trials (RCTs) were retrieved from Pubmed, Embase, and Cochrane Library to evaluate the effects of HDDT and BQT on H. pylori infection from 2002 to August 31, 2022 (last 20 years). A meta-analysis was conducted using Review Manager 5.4 and dichotomous data were estimated by the risk ratio (RR) and the 100% confidence interval (CI). A heterogeneity test and publication bias adjustment were carried out using Stata 12.0.

5604 participants from 14 RCTs were included in this meta-analysis. The eradication rates of H. pylori in the HDDT group and the BQT group were 87.46% and 85.70%, respectively. There was a bordered significant difference (RR = 1.02, 95% CI: 1.00 ~ 1.04, P = 0.03) in the intention-to-treat (ITT) analysis. Inconsistently, in per-protocol (PP) analysis, HDDT showed similar efficacy to BQT (89.97% vs 89.82%, RR = 1.00, 95% CI: 0.99 ~ 1.02, P = 0.67). HDDT showed fewer frequent adverse events than BQT (13.00% vs 31.05%, RR = 0.41, 95% CI: 0.33 ~0.50, P < 0.00001). After adjusting for publication bias, the tendency did not change (RR = 0.49, 95% CI: 0.44 ~ 0.55, P < 0.00001). The compliance of the HDDT group has no significant difference compared with the BQT group (95.88% vs 93.84%, RR = 1.01, 95% CI: 1.00 ~ 1.03, P = 0.14).

HDDT achieved a non-inferiority eradication rate, fewer side effects, and similar compliance compared with BQT.

Background: Currently, the management of Helicobacter pylori (H. pylori) infection in elderly patients is controversial. We investigated whether high-dose dual therapy would serve as the first-line therapy in elderly patients. Methods: This was a single-center, randomized study of 150 elderly patients with H. pylori infection who were randomly assigned to 14-day therapy with pantoprazole 40 mg 3 times daily and either amoxicillin 1,000 mg 3 times daily or amoxicillin 1,000 mg twice daily, clarithromycin 500 mg twice daily and bismuth 220 mg twice daily. H. pylori eradication was evaluated by a 13C-urea breath test 4 weeks after the completion of treatment. Results: Successful eradication was achieved in 89.3% of the high-dose dual therapy (HT) group in the intention-to-treat (ITT) analysis, 91.7% in the modified intention-to-treat (mITT) analysis, and 93.0% for per-protocol (PP) analysis which was similar to the bismuth-containing quadruple therapy (BQT) group (86.6%, 87.8%, and 90.3%, respectively). There were no significant difference between the HT group and the BQT group in the ITT analysis (p = 0.484), mITT analysis (p = 0.458), or PP analysis (p = 0.403). HT was associated with fewer side effects (10.6% of patients) than BQT (26.6%) (p = 0.026). Conclusion: In this trial, we found that 14-day HT had a similar eradication rate to BQT but fewer side effects, which may be better for elderly patients.

Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT.

A systematic review and meta-analysis was conducted.

PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness.

A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive.

Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori, with fewer adverse effects and similar compliance.

Open Science Framework registries (No: osf.io/th4vd).

Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national consensus in China, dual therapy (DT) comprising an acid suppressor and amoxicillin has also been recommended. In recent years, the eradication rate of H. pylori has reached >90% using DT, which has been used not only as a first-line treatment but also as a rescue treatment. Compared with BQT, DT has great potential for H. pylori eradication; however, it has some limitations. This review summarizes the development of DT and its application in H. pylori eradication. The H. pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy, especially in the first-line treatment. The incidence of adverse events associated with DT was lower than that with other therapies. Furthermore, there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology. In the short term, H. pylori eradication causes certain fluctuations in the gastrointestinal microbiota; however, in the long term, the gastrointestinal microbiota eventually returns to its normal state. In the penicillin-naïve population, patients receiving DT have a high eradiation rate, better compliance, lower incidence of adverse reactions, and lower primary and secondary resistance to amoxicillin. These findings suggest the safety, efficacy, and potential of DT for H. pylori eradication.

We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China.

A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by ¹³ C urea breath test (¹³ C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method.

The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of ¹³ C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured.

The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of ¹³ C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.