Amoxicillin Dual Therapy Research Articles

Helicobacter pylori: High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori (H. pylori ) eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for H. pylori eradication in an Irish cohort. AIM To assess the efficacy of HDADT therapy for H. pylori eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with H. pylori . METHODS All patients testing positive for H. pylori in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g tid and esomeprazole 40 mg bid × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior H. pylori treatment. RESULTS One hundred and ninety-eight patients were identified with H. pylori infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% (n = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) vs 62% (58/93), P = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status. CONCLUSION Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.

Helicobacter pylori eradication with high-dose proton pump inhibitor-amoxicillin dual therapy: A systematic review and meta-analysis

BackgroundResistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent. AimsThis study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study. MethodsSeveral open public databases, including Cochrane, EMBASE, PubMed, and MEDLINE, were searched. The results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapies were analysed. Notably, 14 out of the 16 included studies were conducted in Asian regions. ResultsThe eradication rate of HDDT was lower but not significantly different from those of control therapies (odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.67–1.26) in the intent-to-treat (ITT) analysis. A similar trend was observed in the per-protocol (PP) analysis (OR = 0.88, 95% CI = 0.47–1.63). Notably, the adverse effect risk in HDDT was significantly lower than in other therapies (I2 = 67.75%, OR = 0.42, 95% CI = 0.33–0.54, P = 0.00004). When the eradication rate of the control group was lower than 81%, HDDT was significantly better than control therapies (OR = 2.44, 95% CI = 1.23–4.84). ConclusionHDDT used four times a day for 14 days showed better efficacy and safety than the guideline treatments for H. pylori infection in areas with high antimicrobial resistance.

Vonoprazan and amoxicillin dual therapy for 14 days as the first-line treatment of Helicobacter pylori infection: A non-inferiority, randomized clinical trial.

We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.

The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis.

With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.

Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis

Introduction: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication. Methods: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis. Results: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7–91.5% and 88.5% (95% CI: 83.2–93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97–1.10) and 1.02 (95% CI: 0.98–1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05–1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03–1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85–0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73–1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01). Conclusions: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

A "new" option in Helicobacter pylori eradication: High-dose amoxicillin dual therapy outperforms bismuth quadruple therapy in a high dual resistance setting.

Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. Prospective randomized study including 100 consecutive patients undergoing H.pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p= .022) and per-protocol (PP) (95.9% vs. 81%; p= .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p= .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p= .254) and PP (4.8% vs. 0%; p= .210) analysis. When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H.pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.

The Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis.

The eradication of Helicobacter pylori (H. pylori) infection remains challenging due to increasing bacterial resistance. Resistance rates to clarithromycin, metronidazole, and levofloxacin were higher than 30% in the USA, making current therapies less effective. Vonoprazan triple therapy (VAC) has demonstrated similar efficacy and safety profiles compared to PPI-based triple therapy (PPI). However, the eradication rate of vonoprazan dual therapy (VA) for H. pylori infection in comparison to VAC, and PPI was poorly established. Electronic databases were searched up to 6 October 2022, to identify studies examining the safety and efficacy of VA compared to VAC and PPI. Six studies were included. For empiric therapies among treatment naïve patients, VA, VAC, and PPI did not achieve high cure rates (>90%). The comparative efficacy ranking showed VAC was the most effective therapy, followed by VA, and PPI. The results were similar for clarithromycin-resistant infections. The comparative safety ranking showed VA ranked first, whereas PPI triple therapy was the least safe regimen. These findings should guide the selection of the most effective and safe treatment and conduct additional studies to determine the place of vonoprazan dual versus triple therapies in patients with H. pylori from various countries across the world.

Vonoprazan and high-dose amoxicillin dual therapy for Helicobacter pylori first-line eradication: A single-arm, interventional study.

To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high-dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first-line treatment. This prospective, dual-center, single-arm interventional study was performed in Japan. Twenty H. pylori-positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). The intention-to-treat and per-protocol eradication rates were 90% (95% confidence interval [CI] 68.3-98.8%, n=20) and 94.4% (95% CI 72.7-99.9%, n=18) respectively. No significant adverse event was recorded. Vonoprazan/high-dose amoxicillin dual therapy can be a safe standard first-line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan-based triple therapy.

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

Background:High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.Methods:This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov, NCT04678492.

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Comparison of Vonoprazan and Amoxicillin Dual Therapy with Standard Triple Therapy with Proton Pump Inhibitor for Helicobacter Pylori eradication: A Randomized Control Trial.

Objectives:To compare the efficacy of Vonoprazan based dual treatment versus PPI based treatment for the eradication of Helicobacter pylori infection.Methods:A randomized controlled trial was conducted in Department of Medicine/Gastroenterology Ruth KM Pfau Civil Hospital, DMC during the period of 22 June to 21 September 2021. Sample size was calculated as 96 in each Group. All patients of age 18-75 years with Helicobacter Pylori Infection were inducted and randomly allocated to two groups. Group-A: were given Capsule Amoxicillin 1 gm; Tablet Clarithromycin 500 mg; Capsule Omeprazole 20 mg all medications were given twice daily for two weeks. Group-B were given Capsule Amoxicillin 1 gm; Tablet Vonoprazan 20 mg (Vonozon©, m/s Getz Pharma, Pakistan) twice daily for two weeks. Confirmation of Hp eradication was done by stool Hp antigen test four weeks after completion of treatment. Nine and four patients were lost to follow-up in Group-A & B respectively. Analysis was conducted on 87 patients in Group-A and 92 patients in Group-B.Results:Out of eighty-seven patients in Group-A and ninety-two patients in Group-B, 73 (83.9%) patients in Group-A and 86 (93.5%) patients in Group-B had negative H pylori result respectively after treatment (p = .042). Significantly higher frequencies of adverse events were observed in Group-A as compared to Group-B in nausea/vomiting (p = .035) and bloating (p = .045).Conclusion:VA-dual provides an acceptable eradication rate with fewer adverse events.

Efficacy and safety of high-dose esomeprazole and amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori infection: a multicenter, randomized controlled clinical trial.

A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori (H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials. To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection. A multicenter, open-label, randomized controlled clinical trial. Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance. The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%). HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection. This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096).

High-dose dual therapy versus culture-based susceptibility-guided therapy as a rescue regimen for Helicobacter pylori infection: a randomized controlled trial.

Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking. To compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection. A single-center, open-label, randomized controlled clinical trial. In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days. The eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT. HDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection. This clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

High‐dose proton pump inhibitor and amoxicillin dual therapy with or without bismuth for 14 days as rescue therapies after Helicobacter pylori treatment failure

ObjectiveHelicobacter pylori (H. pylori) treatment failures are difficult to treat. In this study we aimed to test the efficacy of two high‐dose dual therapy regimens with or without bismuth for 2 weeks as a rescue therapy for patients with previous H. pylori treatment failure.MethodsH. pylori‐positive patients were randomly assigned to either dexlansoprazole 60 mg twice a day and amoxicillin 1 g 4 times a day without (high‐dose dual therapy [HDDT]) or with colloidal bismuth subcitrate 240 mg twice a day (HDDT‐Bi) for 14 days. Eradication of H. pylori was tested using the 13C‐urea breath test at least 4 weeks (HDDT) or 8 weeks (HDDT‐Bi) after the completion of therapy.ResultsH. pylori was eradicated in 84.6% (33/39) of patients (95% confidence interval [CI]: 70.3‐92.8%) in the HDDT group, compared with 80.5% (33/41) (95% CI: 66.0‐89.8%) in the HDDT‐Bi group on an intention‐to‐treat (ITT) analysis, and in 89.2% (33/37) (95% CI: 75.3‐95.7%) in the HDDT group compared with 82.5% (33/40) (95% CI: 68.1‐91.3%) in the HDDT‐Bi group on a per‐protocol (PP) analysis. There was no significant difference in the eradication rates in both groups on ITT and PP analysis. Both treatment regimens were well tolerated.ConclusionsAdding bismuth to HDDT did not increase H. pylori eradication rates after treatment failure. HDDT and HDDT‐Bi achieved a satisfactory eradication rate of more than 80% as rescue therapies. Both treatment regimens were well tolerated by patients and compliance with treatment was good.

Vonoprazan-containing Helicobacter pylori triple therapies contribution to global antimicrobial resistance.

Amoxicillin and proton pump inhibitor dual Helicobacter pylori therapy has proved not to be reliably highly effective primarily because of traditional proton pump inhibitors' inability to maintain a high intragastric pH. Clarithromycin and proton pump inhibitor H.pylori dual therapy failed in part because clarithromycin resistance emerged during therapy causing treatment failures. The combination of amoxicillin, clarithromycin, and proton pump inhibitor was subsequently undermined by increasing clarithromycin resistance. Although vonoprazan appeared to restore the effectiveness of triple therapy, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in the majority (>85% currently in Japan) of those receiving vonoprazan-amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin) receiving no benefit from the second antibiotic. The results in somewhere between 2800 and 5600kg of unnecessary clarithromycin per one million H.pylori treatment courses per year in Japan. The only contribution of the second antibiotic is to increase global antimicrobial resistance. There are now sufficient data to prove that optimized vonoprazan-amoxicillin dual therapy can reliably achieve cure rates≥95%. This manuscript discusses use of the principles of antimicrobial stewardship to develop potassium-competitive acid blocker-containing H.pylori therapies that will reliably achieve high H.pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently needed so that use of vonoprazan triple therapies can be curtailed while also improving overall H.pylori cure rates.

Comparative study of H.pylori eradication rates of high and frequent dose of Omeprazole and Amoxicillin dual therapy versus standard triple therapy in children

Comparative study of H.pylori eradication rates of high and frequent dose of Omeprazole and Amoxicillin dual therapy versus standard triple therapy in children

Comparative study of H.pylori eradication rates of high and frequent dose of Omeprazole and Amoxicillin dual therapy versus standard triple therapy in children

Objectives and Study: With increasing prevalence of clarithromycin and metronidazole resistant H. pylori strains, eradication rates with triple therapy have fallen below 80% worldwide. Unlike that to clarithromycin or metronidazole, H.pylori resistance to amoxicillin(AMO) remains uncommon. AMO is also unique in that its bactericidal effect against H. pylori is time dependent (6-8 h after administration) and can be amplified by increasing the maximum intragastric pH(>6.5) using high-dose proton pump inhibitor( PPI) .High-dose dual therapy, of a PPI and …

Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan

ObjectiveTo date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy...

Efficacy and safety of high-dose dual therapy for Helicobacter pylori rescue therapy: A systematic review and meta-analysis.

Although some studies have reported >90% success with high-dose dual proton pump inhibitor (PPI)-amoxicillin dual therapy for Helicobacter pylori (H. pylori) eradication, the efficacy of this therapy remains controversial. We aimed to re-evaluate the efficacy and safety of high-dose dual therapy on H. pylori eradication. We searched PubMed, the Cochrane Library, and EMBASE for randomized clinical trials (RCTs) evaluating the efficacy of high-dose PPI-amoxicillin dual therapy as the rescue therapy on H. pylori eradication. Treatment effect was determined with a fixed-effect model using the inverse variance method and was expressed as risk ratio (RR) with 95% confidence interval (CI). Because of significant statistical heterogeneity (χ2 15.98, I2 = 69%) among the six studies that qualified, four RCTs that included 473 patients with H. pylori infection after eradication failure were assessed. The meta-analysis showed that high-dose dual therapy and guideline-recommended rescue therapies achieved similar efficacy (81.3% vs 81.5%, RR 1.00 [95% CI 0.93-1.08], intention-to-treat analysis), compliance (95.3% vs 95.4%, RR 1.00 [95% CI 0.97-1.03]), and side effects (17.9% vs 19.7%, RR 0.88 [95% CI 0.62-1.25]). High-dose PPI-amoxicillin dual therapy is comparable to recommended rescue therapies for H. pylori infection. More researches are needed to determine the efficacy of high-dose dual therapy as a first-line therapy.