Introduction

​​​​Helicobacter pylori (H.pylori) is a persistent public health issue that contributes to a number of gastrointestinal pathologies such as peptic ulcer disease and gastric cancer. Standard triple therapy is the first line of treatment, but the efficacy is unsatisfactory. Moreover, antibiotic resistance is expanding. Statin is recently discovered to improve the in vitro efficacy of H. pylori eradication by decreasing pathogen adhesion and promoting autophagy in human macrophages, resulting in a in H.pylori burden and inflammation.

Aims & Methods

Aims: To evaluate the efficacy and safety of adding atorvastatin as an adjuvant therapy to the standard triple therapy compared with the standard triple therapy for patients with H. pylori infection.
Methods: A randomized, double-blind placebo controlled trial is conducted. 108 patients with H. pylori infection are randomized into 2 groups. 55 patients in the intervention group are treated with a 14-days OAC-S regimen (omeprazole 20 mg bid, amoxicillin 1,000 mg bid, clarithromycin 500 mg bid, atorvastatin 40 mg OD). 53 patients in the control group are treated with a 14-days OAC-P regimen (omeprazole 20 mg bid, amoxicillin 1,000 mg bid, clarithromycin 500 mg bid, placebo atorvastatin). The eradication evaluated by a ¹⁴C-urea breath test (UBT) is the primary outcome. CYP2C19 and CYP3A4/5 genotypes, side effects and patient compliance are also evaluated.

Results

H.pylori eradication rate The eradication rate by per-protocol analysis is considerably higher in the intervention group (98.1%) than in the control group (84.9%) and the risk difference is 0.13 (95% CI 0.03-0.25, P=0.02). In addition, intention to treat analysis shows that the eradication rate is higher in the intervention group (96.36%) than in the control group (84.9%) and risk difference of 0.11 with statistical significance (95% CI 0.00-0.24, P=0.05).

Treatment outcome 14C-urea breath test	Control group OAC+P (n=53)	Intervention group OAC+S (n=54, loss to follow up =1)	Risk difference
Failure, n (%)	8 (15%)	1 (1.85%)
Success, n (%)	45 (84.90%)	53 (98.10%)
Eradication rate (%) *PP analysis	84.9 %	98.1%	0.13 95%CI: 0.03-0.25 p-value = 0.02
Treatment outcome 14C-urea breath test	Control group OAC+P (n=53)	Intervention group OAC+S (n=55)	Risk difference
Failure, n (%)	8 (15%)	2 (3.64%)
Success, n (%)	45 (84.90%)	53 (96.36%)
Eradication rate (%) **ITT analysis	84.9%	96.36%	0.11 (95% CI: 0.00-0.24) p-value= 0.05

^{*Per-protocol analysis: only subjects who are adherent to the treatment (>85%) and complete the follow-up at their original group allocation.
**Intention to treat analysis: All randomized patients are included irrespective of their compliance with treatment or lost to follow-up. Subjects who lost the follow-up = failure to treatment}

CYP status of both groups There are no significant differences in CYP2C19 and CYP3A4/5 genotype status between both groups.
Adverse events Minor adverse effects have been reported in bitter taste for 49.1% in all patients without significant difference between both groups. Myositis is higher in intervention group (29.6%) than the control group (17.0%), however, there is no clinical symptoms and statistical significance. Mild transaminitis is slightly higher in the intervention group (29.6%) than the control group (20.8%); howbeit, there is no clinical symptoms and statistical significance.

Conclusion

Adjuvant therapy with atorvastatin, in conjuction with standard triple therapy significantly increases the eradication rate of H.pylori infection without clinically important adverse events. With respect to the limitations of this study (limited number of cases in one center), further studies or extended studies will be helpful in clarifying the effects of statin on H.pylori treatment.

References

1. James KH, Wan YL, Wee KNg, et al.Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153:420–9.
2. Chunlertlith K, Limpapanasit U, Mairiang P, et al. Outcomes of a Randomized Controlled Trial Comparing Modified High Dose Omeprazole and Amoxicillin Triple Therapy with Standard Triple Therapy for Helicobacter Pylori Eradication. Asian Pac. J. Cancer Prev. 2017;18:927-32.
3. Vilaichone RK, Gumnarai P, Ratanachu-Ek T, et al.Nationwide survey of Helicobacter pylori antibiotic resistance in Thailand. Diagnost Microbiol Infect Dis. 2013;77(4):346-9.
4. Jan HM, Chen YC, Yang TC, et al. Muthusamy S et al. Cholesteryl α-D-glucoside 6-acyltransferase enhances the adhesion of Helicobacter pylori to gastric epithelium. Commun. Biol. 2020;3:120.
5. Liao WC, Huang MZ, Wang ML, et al. Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy. Front Cell Infect Microbiol. 2017;6:20313.

Introduction

Potassium-competitive acid blockers (P-CABs) offer prolonged acid suppression and are promising agents for Helicobacter pylori eradication. Prospective studies evaluating the efficacy of tegoprazan-based triple therapy according to dosage differences have been scarce.

Aims & Methods

This study aimed to assess the efficacy and safety of tegoprazan-based versus lansoprazole-based standard triple therapy (STT). This multicenter randomized controlled study enrolled treatment-naïve adults with H. pylori infection in 18 institutions from February 2023 to April 2024. Participants were randomized 1:1:1 to receive tegoprazan 50 mg (TAC1), tegoprazan 100 mg (TAC2), or lansoprazole 30 mg (LAC) with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 14 days. The primary endpoint was the eradication rate, analyzed in the full analysis set (FAS) and per-protocol set (PPS). Secondary endpoints included eradication rates stratified by clarithromycin resistance, as determined by 23S rRNA genotyping. Non-inferiority was established if the lower bound of the 95% confidence interval (CI) for the difference in eradication rates was greater than -10%.

Results

A total of 382 patients were randomized, of whom 364 completed the study. The FAS included 372 participants after excluding those who did not receive any study medication, lacked safety data, or violated eligibility criteria. The PPS comprised 355 participants after excluding 17 protocol violators. In the FAS analysis, eradication rates were 85.95% for TAC1, 85.48% for TAC2, and 78.74% for LAC. Both TAC1 (p = 0.0002 vs. LAC) and TAC2 (p = 0.0003 vs. LAC) demonstrated non-inferiority. In the PPS analysis, eradication rates were 88.50% for TAC1, 87.39% for TAC2, and 81.30% for LAC, with TAC1 (p < 0.0001 vs. LAC) and TAC2 (p = 0.0003 vs. LAC) maintaining non-inferiority. Among 275 clarithromycin-susceptible patients in the PPS, eradication rates were 96.74% (TAC1), 98.88% (TAC2), and 94.68% (LAC). Among 80 clarithromycin-resistant patients, eradication rates were 52.38% (TAC1), 53.33% (TAC2), and 37.93% (LAC). In both subgroups, there were no significant differences between either TAC1 or TAC2 and the LAC group. Adverse event rates were comparable across groups, and no serious adverse events were reported. No significant differences in adverse event rates were observed across groups, and no serious adverse events occurred.

	TAC1 group	TAC2 group	LAC group
FAS, n	121	124	127
Successful H. pylori eradication, n (%)	104 (85.95%)	106 (85.48%)	100 (78.74%)
Difference from LAC group (95% CI)	7.21 (-2.22, 16.64)	6.74 (-2.69, 16.18)
p-value	0.0002	0.0003
PPS, n	113	119	123
Successful H. pylori eradication, n (%)	100 (88.5%)	104 (87.39%)	100 (81.30%)
Difference from LAC group (95% CI)	7.19 (-1.87, 16.26)	6.09 (-3.02, 15.21)
p-value	<0.0001	0.0003

Conclusion

Tegoprazan-based STT demonstrated non-inferiority to lansoprazole-based STT, achieving eradication rates above 80% in the FAS population. Given its efficacy and safety profile, tegoprazan-based triple therapy may serve as an effective first-line treatment option for H. pylori eradication.

Disclosure

This study was funded in full by HK inno.N Corp., Seoul, Republic of Korea. HK inno.N Corp. contributed to the study design, data management, statistical analysis, and approval of publication in co-operation with all the authors. No other potential conflicts of interest relevant to this article were reported.

Introduction

Helicobacter pylori (Hp) infection remains a major public health problem, associated with significant morbidity and mortality, whose eradication therapy has proven to be effective in preventing these complications.^1,2 Given the high resistance to antibiotics and the scarcity of available antibiotic therapy worldwide, there is not enough data on the best eradication strategy.^3,4

Aims & Methods

Aim: The aim of this study was to perform a comparative evaluation of the efficacy and safety of the different quadruple therapy regimens currently recommended for the Hp eradication, including Esomeprazole 40 mg bid.
Methods: A blind randomized controlled clinical trial of consecutive patients with gastric infection by Hp, diagnosed by 13C-urea breath test (UBT) or histological analysis were randomized in 5 therapy arms (A: Quadruple with metronidazole 500 mg tid, 14 days; B: Quadruple with metronidazole 500 mg bid, 14 days; C: Quadruple with bismuth, 10 days; D: Sequential, 7 days; E: Hybrid, 7 days). Hp eradication with evaluation of the efficacy and safety rates at 1-2 months after the eradication therapy was made.

Results

From a total of 200 patients currently included, 193 concluded the protocol study (164-histological analysis; 29-UBT), 102 males (52.8%), mean age of 57.2±16.3 (A: 38; B: 39; C: 38; D: 41; E: 37). Overall efficacy rate of quadruple therapy regimens was 95.9% (n=185), being 100.0% for arm A, 92.3% for arm B, 97.3% for arm C, 97.6% for arm D and 91.9% for arm E (p=0.431). Overall adverse events rate of quadruple therapy regimens was 53.9% (n=104), being diarrhea (27.5%) and nausea (26.9%) the most common. Major symptoms (need for therapy or impairment of daily living activities) occurred in 8.3%. Adverse events/Major adverse events rates for the different regimens were 50.0%/5.3% for arm A, 69.2%/15.4% for arm B, 48.6%/7.9% for arm C, 48.8%/4.9% for arm D and 54.0%/8.1% for arm E (p=0.287/p=0.451).

Conclusion

In Portugal, all the quadruple therapy regimens currently recommended for the eradication of Hp, with or without bismuth, have been effective in eradicating Hp gastric infection. However, concomitant therapy with metronidazole bid seems to have a higher rate of adverse effects, including major adverse effects.

References

1. Zamani, M., Ebrahimtabar, F., Zamani, V., et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2018; 47(7): 868-876.
2. Malfertheiner, P., Megraud, F., O’Morain, C.A., et al. Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut 2017; 66(1): 6-30.
3. Savoldi, A., Carrara, E., Graham, D.Y., et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155(5): 1372-1382.
4. Lopo, I., Libânio, D., Pita, I., et al. Helicobacter pylori antibiotic resistance in Portugal: Systematic review and meta[1]analysis. Helicobacter 2018; 23(4): e12493.

Disclosure

Nothing to declare.

Introduction

Helicobacter pylori is a common cause of peptic ulcers and gastritis. Standard triple therapy includes a PPI with amoxicillin and either clarithromycin or levofloxacin. Rising antibiotic resistance has reduced its effectiveness. Sequential therapy offers a phased alternative with better outcomes in resistant cases.

Aims & Methods

To evaluate and compare the efficacy of clarithromycin and levofloxacin-based triple and sequential therapies for Helicobacter pylori (H. pylori) eradication in a resource-limited setting, in the context of emerging antibiotic resistance.
A prospective, randomized study was conducted at a tertiary care center from January 1, 2022, to January 1, 2025. A total of 300 treatment-naïve patients aged 18–60 years, diagnosed with H. pylori infection through stool antigen, urea breath test, or histology, were included. Patients with prior eradication therapy or recent antibiotic use were excluded. Participants were randomized into four equal groups (n=75 each):

• Clarithromycin-based triple therapy (amoxicillin, clarithromycin, PPI)
• Levofloxacin-based triple therapy (amoxicillin, levofloxacin, PPI)
• Clarithromycin-based sequential therapy (amoxicillin + PPI for 5 days, followed by clarithromycin + tinidazole + PPI for 5 days)
• Levofloxacin-based sequential therapy (amoxicillin + PPI for 5 days, followed by levofloxacin + tinidazole + PPI for 5 days) Therapeutic response was assessed post-treatment for eradication.
  

Results

Out of 300 patients (180 males, 120 females), eradication was achieved in:

• 48/75 (64%) in clarithromycin-based triple therapy
• 53/75 (70.7%) in levofloxacin-based triple therapy
• 51/75 (68%) in clarithromycin-based sequential therapy
• 61/75 (81.3%) in levofloxacin-based sequential therapy

All patients completed therapy without notable adverse events or compliance issues. Lower eradication rates in clarithromycin-based regimens suggest rising resistance.

Conclusion

Levofloxacin-based sequential therapy demonstrated the highest eradication rate, highlighting its potential as a preferred regimen in settings with rising clarithromycin resistance. Clarithromycin-based treatments showed suboptimal outcomes, emphasizing the need for region-specific antibiotic stewardship and resistance surveillance.

References

1. Kim JS, Kim BW, Hong SJ, Kim JI, Shim KN, Kim JH, Baik GH, Kim SW, Song HJ, Kim JH. Sequential Therapy versus Triple Therapy for the First Line Treatment of Helicobacter pylori in Korea: A Nationwide Randomized Trial. Gut Liver. 2016 Jul 15;10(4):556-61. doi: 10.5009/gnl15470. PMID: 27114421; PMCID: PMC4933415.
2. Chang, J.Y., Shim, KN., Tae, C.H. et al. Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication. BMC Gastroenterol 17, 16 (2017). https://doi.org/10.1186/s12876-017-0579-8

Introduction

It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to Vonoprazan-amoxicillin dual therapy as a first-line treatment can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. Therefore, we conducted the randomized controlled trials (RCTs) to address this issue.

Aims & Methods

This is a single-center, prospective randomized controlled study. A total of 150 eligible patients, recruited from December 2023 to November 2024, were randomly assigned to the VA (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily for 10 days) and VAS groups (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily, and S. boulardii 250 mg twice daily for 10 days). The eradication rates, adverse events, safety, and compliance were compared between the two groups. Factors associated with eradication rate were explored.

Results

The eradication rates of VA and VAS were 89.3% and 93.3%, respectively, by intention-to-treat analysis (P = 0.384); 93.1%, and 94.6%, respectively, by per-protocol analysis (P=0.966). The incidence of adverse events significantly lower in the VAS group (5.4%) than in the VA group (22.2%; P=0.003). There was no significant difference in compliance between the VA (96%) and VAS groups (98.7%, P = 0.612). Body surface area (BSA) was found to be a influencing factor for eradication rate in both VA and VAS groups. Serum chemistry tests revealed no significant differences in liver and kidney function before and after treatment in both groups.

Conclusion

Although the addition of S. boulardii to VA dual therapy could not increase the eradication rate, it could decrease the incidence of adverse events. Low-BSA patients are more suitable candidates for this regimen.

Introduction

14-day non-bismuth concomitant (with amoxicillin, clarithromycin and metronidazole) and Bismuth-based quadruple therapy are recommended first-line empirical treatment for Helicobacter pylori (H. Pylori) eradication. Systematic use of susceptibility testing and tailored first-line treatment remains to be established.

Aims & Methods

We did a multicentre, parallel group, randomised controlled trial at five French centres. Adult (≥18 years) patients with H. pylori infection were randomly assigned to verify non-inferiority of 14-day tailored PCR-guided triple therapy (tailored EAC/L14: esomeprazole 40 mg, amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for clarithromycin susceptible strain or levofloxacin 500 mg twice daily for clarithromycin resistant strain) compared to 14-day non-Bismuth concomitant quadruple therapy (EACM14: esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg and metronidazole 500 mg twice daily). The primary endpoint was H. pylori eradication assessed by ¹³C urea breath test done 6 to 12 weeks after treatment. Analyses were performed in the intention-to-treat (ITT) and the per protocol (PP) populations, considering a prespecified expert-based non-inferiority margin of -5%.

Results

We screened 991 patients for eligibility and randomised 241 patients to received EACM14 or tailored EAC/L14. In the per-protocol population (excluding patients who did not performed ¹³C–urea breath test 6-12 weeks after eradication therapy and/or did not received a full 14-day regimen treatment), the eradication rate was 98.8% in the 14-day tailored PCR-guided triple therapy arm vs 96.5% in the 14-day non-Bismuth concomitant quadruple therapy arm, with the difference between the two groups being +2.35% (lower bound of CI at -3.33%). The first-line eradication rate (primary endpoint) in the ITT population was 99.2% in the tailored EAC/L14 PCR-guided group and 95.9% in the EACM14 control group, with the difference being +3.30% (lower bound of confidence interval (CI) at -0.68%). Both ITT and PP analyses demonstrated non-inferiority of EAC/L14 group, with unilateral CI95% lower bounds superior to the prespecified margin. Both first-line therapies were well tolerated, with a significant difference in favour of the tailored EAC/L14 group (any adverse events: 61.4% [EACM14] vs 41.2% [EAC/L14], p = 0.003). The most common adverse event involved the gastrointestinal tract in 107 (46.9%) patients, including 66 (57.9%) patients in the control arm and 41 (36.0%) in the experimental arm (p = 0.001).

Conclusion

In a country with high level of clarithromycin resistance, we showed the non-inferiority of 14-day tailored PCR-guided triple therapy as first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov, number NCT02576236.).

Introduction

The Helicobacter pylori (H. pylori) infection is a common problem (prevalence of 32.7% in 2023) in the North-Western Federal District, comprising one-tenth of Russia, where primary resistance rates of clarithromycin and levofloxacin are >15%.¹ The eradication rates remain low and do not reach the threshold value of 95% (eradication rate of 86.8% in 2023). ² There is limited information regarding the best approach for H. pylori infection management.

Aims & Methods

The study was conducted in the North-Western Federal District during 2023-2025. Individuals (n=145) who underwent ¹³C-UBT (¹³С-urea breath test) was conducted in the prospective randomized clinical trial. Patients were randomly allocated to two eradication groups: high-dose dual therapy for 14 days (esomeprazole 40 mg and amoxicillin 1000 mg three times daily) and optimized high-dose dual therapy for 14 days (esomeprazole 40 mg, amoxicillin 1000 mg, rebamipide 100 mg three times daily). The modified intention-to-treat (mITT) effectiveness, safety, and adherence were analyzed for the regimens. The secondary endpoints were adverse effects and patient compliance. Eradication was confirmed by a ¹³C-UBT 4-6 weeks after therapy.

Results

Among all included individuals (mean age 46.27±14.21; 67.6% of whom were female), there were 91.7% (n=133) of primary “naïve” patients (who had had no history of prior eradication therapy). The proportion of treated patients was 8.3% (n=12). The high-dose dual therapy PPI-amoxicillin did not provided encouraging mITT results - 87.5%, 21/24, 95%CI 69.0-95.7; the inclusion of patients in this group was stopped due to unacceptable cure rates. Whereas the higher was reported with optimized eradication regimen with rebamipide (96.3%, 105/109, 95%CI 90.9-98.6 for treatment-naïve and 91.7%, 11/12, 95%CI 64.9-98.5 for treated patients). The adverse event rates were 37.5% in the PPI-amoxicillin group and 19.8% in the PPI-amoxicillin-rebamipide group (р=0.211). The most common were a diarrhea (25% and 12.4% respectively), bloating (25% and 3.5% respectively), abdominal pain (20.8% and 10.7% respectively). Good adherence, defined as > 90% of drug intake, were similar between the two groups (100% of cases).

Conclusion

In the North-Western region of Russia, the fourteen-day optimized high-dose dual therapy with PPI-amoxicillin-rebamipide provided encouraging results (over 90% cure rates) and had the lower incidence rate of side effects (19.8%) suggesting as an alternative for H. pylori rescue treatment in the local region.

References

1. Simanenkov VI, Zakharova NV, Zhebrun AB, et al. Resistance of Helicobacter pylori to antimicrobial preparations by the results of bacteriologic testing. Attending Physician. 2015;4:10 (In Russ.)].
2. Bakulina NV, Tikhonov SV, Savilova IV, Zharkov AV, Ponomarenko VA. Dynamics of the prevalence of Helicobacter pylori infection from 2015 to 2023. Herald of North-Western State Medical University named after I.I. Mechnikov. 2023;15(3):41–51. DOI: https://doi.org/10.17816/mechnikov623259