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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 of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.DesignThis prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori–positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.ResultsBetween October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.ConclusionThe 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.Trial registration numberUMIN000034140.

Among 1676 persons with H. pylori infection who had family members with gastric cancer, the incidence of gastric cancer over a median follow-up of 9.2 years was significantly lower among those who received eradication treatment for H. pylori infection than among those who received placebo.

Among patients with endoscopically resected early gastric cancers who were infected with Helicobacter pylori , the incidence of metachronous gastric cancer was 50% lower among those who received active treatment with antibiotics than among controls.

Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6–92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7–88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4–86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7–10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

This study assessed the effectiveness, adverse events, patient adherence, and costs of modified dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients. We also sought to determine whether modified dual therapy could be used as an alternative first-line treatment for H. pylori infection. A total of 232 H. pylori-infected, treatment-naive patients were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day modified dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the 2 groups. The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, per-protocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar compared with the bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%. In addition, modified dual therapy ameliorated variations in the CYP2C19, IL-1B-511, and H. pylori VacA genotypes. There were no significant differences in the compliance rates between the 2 groups. The modified dual therapy group exhibited significantly less overall side effects compared with the bismuth-containing quadruple therapy group (P < 0.001). Furthermore, the cost of medications in the modified dual therapy was lower compared with that in the bismuth-containing quadruple therapy. Modified dual therapy at high dose and administration frequency is equally effective and safer and less costly compared with bismuth-containing quadruple therapy.

ObjectiveTo evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy.DesignSubjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial.ResultsTwo hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (eg, susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group.ConclusionsThese results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains.Trial registration numberNCT02175901.

Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action under clinical development for the treatment of Helicobacter pylori infection. We aimed to evaluate the efficacy and safety of a rifasutenizol-based triple therapy (RTT) versus bismuth plus clarithromycin-based triple therapy (BCTT) for the treatment of H pylori infection in treatment-naive patients. EVEREST-HP was a phase 3, randomised, triple-dummy, double-blind, active-controlled, non-inferiority trial with adaptive design for sample size re-estimation conducted at 40 research hospitals in China. Treatment-naive patients aged 18–65 years, with a positive [13C]urea breath test ([13C]UBT), further confirmed by gastric biopsy and histological examination, were randomly assigned (1:1) to receive RTT (rifasutenizol 400 mg oral capsules, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tables) or BCTT (bismuth potassium citrate 240 mg oral tablets, clarithromycin 500 mg oral tablets, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tablets), all twice a day for 14 days. Randomisation was done centrally by a secure interactive web response system using block sizes of two or four and stratified by study site. RTT was compared against BCTT using a triple-dummy approach to ensure masking. The primary endpoint was H pylori eradication rate based on [13C]UBT 4–6 weeks after the end of treatment in the modified intention-to-treat population, which included all participants who received at least one dose of the study drugs. The eradication rates of RTT and BCTT were compared using a one-sided α value of 0·025 and a non-inferiority margin of –10%. Safety endpoints included investigator assessed treatment-emergent adverse events, the severity and relationship with study drugs, findings from physical examinations, vital signs, laboratory tests, and electrocardiogram. An interim analysis was conducted by an independent data monitoring committee after 50% (350) of patients completed the last [13C]UBT. The trial is registered with ClinicalTrials.gov, NCT05857163. Between May 18, 2023, and Nov 10, 2023, 1267 patients were screened and 700 patients were randomly assigned to receive either RTT (n=353) or BCTT (n=347). 261 (37%) patients were men and 439 (63%) were women. 351 patients in the RTT group and 346 in the BCTT group took at least one dose of the study drugs and were included in the modified intention-to-treat group and the safety set. H pylori was successfully cultured from 579 (83%) of 697 patients. 236 (41%) of 579 patients had H pylori infection resistant to clarithromycin, 395 (68%) to metronidazole, 203 (35%) to levofloxacin, and 47 (8%) to amoxicillin. All H pylori clinical isolates were susceptible to rifasutenizol. In the modified intention-to-treat analysis, the H pylori eradication rate in the RTT group was non-inferior to that in the BCTT group (92·0% [95% CI 88·7 to 94·6; 323 of 351] vs 87·9% [83·9 to 91·1; 304 of 346]; absolute difference 4·2% [95% CI –0·3 to 8·8]). 131 (37%) of 351 patients in the RTT group and 184 (53%) of 346 in the BCTT group had treatment-emergent adverse events. Treatment-emergent adverse events occurring in more than 5% of patients in the RTT group were diarrhoea (in 24 [7%] patients), nausea (22 [6%]), and dizziness (21 [6%]), and in more than 5% of patients in the BCTT group were taste perversion (125 [36%]), nausea (21 [6%]), and diarrhoea (19 [5%]) Most of the treatment-emergent adverse events were mild or moderate in severity. No serious adverse event related to study drugs was reported. As the first novel antimicrobial agent specifically developed for H pylori infection, rifasutenizol represents a promising addition to the existing options for tackling antimicrobial resistance, and RTT represents a promising first-line treatment option for H pylori infection. TenNor Therapeutics. For the Chinese translation of the abstract see Supplementary Materials section.

Vonoprazan, a novel and potent acid suppressant, has recently been incorporated into Helicobacter pylori eradication regimens. However, the data on combination of vonoprazan with levofloxacin remains scarce. This study represents one of the first evaluations comparing 7-day and 14-day once-daily regimens containing vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for H. pylori eradication in regions characterized by high clarithromycin and metronidazole resistance. Between March 2022 and December 2023, patients presenting with dyspepsia who underwent upper gastrointestinal endoscopy at a tertiary care hospital in Thailand were recruited. Those testing positive for H. pylori infection were randomly assigned to receive either a 7-day or 14-day once-daily regimen comprising vonoprazan 40 mg, clarithromycin-MR 1 g, levofloxacin 500 mg, and bismuth subsalicylate 1,048 mg. CYP3A4 polymorphism testing and antimicrobial susceptibility assessment (using either the Epsilometer test or the GenoType ® HelicoDR assay) were performed. Eradication was confirmed by a negative ¹³C-urea breath test conducted no sooner than four weeks after completing therapy. A total of 312 dyspeptic patients who underwent EGD were screened, and 102 (32.7%) were diagnosed with H. pylori infection. The study enrolled and randomized these patients into two treatment groups: 51 received the 7-day once-daily vonoprazan-based bismuth therapy, and 51 received the 14-day regimen. Baseline characteristics were similar between the two groups, except for a higher prevalence of hypertension in the 7-day regimen group (49% vs. 27.5%, p  = 0.025). The eradication rates for the 7-day regimen were 88.2% (45/51) in the intention-to-treat (ITT) analysis and 89.6% (43/48) in the per-protocol (PP) analysis. Similarly, the 14-day regimen achieved eradication rates of 88.2% (45/51) in the ITT analysis and 93.8% (45/48) in the PP analysis. The risk difference for eradication in the PP analysis was 4.17% (95% CI: -6.86 to 15.19, p  = 0.71). Adverse events were comparable between the two regimens, occurring in 35.3% (18/51) of patients in the 7-day regimen and 38.8% (19/51) in the 14-day regimen ( p  = 0.130). The most frequently reported adverse event was black stool (35.3% vs. 38.8%, p  = 0.130). Other adverse events included nausea and vomiting (15.7% vs. 22.5%, p  = 0.742), bitter taste (17.7% vs. 18.4%, p  = 1.000), and dizziness (7.8% vs. 6.1%, p  = 0.113). All adverse events resolved spontaneously without requiring medical intervention, and no serious adverse events were reported. The 14-day regimen demonstrated excellent eradication rate (> 90%) regardless of CYP3A4 polymorphisms. These findings suggest that vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for 14 days is a promising alternative first-line treatment option, particularly in regions with high clarithromycin and metronidazole resistance.

A paucity of evidence regarding use of endoscopic sinus surgery and antibiotics in managing chronic rhinosinusitis has contributed to a five-times variation in endoscopic sinus surgery rates, as well as variation in the use of antibiotics. The main aim of the present trial was to compare the clinical effectiveness of endoscopic sinus surgery or 3 months of clarithromycin treatment alongside intranasal medication in adults with chronic rhinosinusitis with or without nasal polyps. In this pragmatic, three-arm, randomised, placebo-controlled phase 4 trial, participants were recruited from 20 secondary and tertiary care sites in the UK. Adults (aged ≥18 years) with chronic rhinosinusitis remaining symptomatic following appropriate medical therapy (intranasal corticosteroids, saline nasal irrigations, and a short course of antibiotics) were randomly assigned (1:1:1) to receive endoscopic sinus surgery (within 6 weeks of randomisation if waiting lists allowed) plus intranasal medication, clarithromycin (250 mg twice a day for 2 weeks then 250 mg once a day for 10 weeks) plus intranasal medication, or placebo plus intranasal medication. Intranasal medication comprised intranasal corticosteroids and saline irrigations. Participants were allocated with an automated, web-based secure randomisation system in permuted blocks of varying size (block sizes of three and six), stratified by the presence of polyps and trial site. Participants and site teams were masked to the clarithromycin and placebo allocations, including for outcome assessment. The primary outcome measure was the total score on the 22-item Sino-Nasal Outcome Test (SNOT-22) quality-of-life questionnaire at 6 months after randomisation, with analysis by intention to treat (ITT; available-case basis). Adverse reactions were assessed in the safety population (clarithromycin and placebo), and serious adverse events in the ITT population (all groups). The trial was registered on the ISRCTN registry, ISRCTN36962030, and EudraCT, 2018-001100-11, and is complete, with optional long-term follow-up ongoing. Between Nov 1, 2018, and Oct 13, 2023, 514 participants (181 [35%] female and 333 [65%] male), with chronic rhinosinusitis with nasal polyps (n=410) or chronic rhinosinusitis without nasal polyps (n=104), were recruited and randomly assigned to receive endoscopic sinus surgery (n=171), clarithromycin (n=172), or placebo (n=171), all with intranasal medication. SNOT-22 scores at 6 months after randomisation were significantly lower (at the 98·33% confidence level after Bonferroni adjustment) in the endoscopic sinus surgery group than in the clarithromycin group (adjusted mean difference –18·13 [98·33% CI –24·26 to –11·99], p<0·0001) and placebo group (–20·44 [–26·42 to –14·46], p<0·0001). 6-month SNOT-22 scores did not differ significantly between participants randomly assigned to clarithromycin versus placebo (–3·11 [–8·56 to 2·33], p=0·17). Ten serious adverse events occurred in nine participants (two events in two [1%] of 172 participants allocated to clarithromycin, three events in three [2%] of 171 allocated to placebo, and five events in four [2%] of 171 allocated to endoscopic sinus surgery), none of which were fatal. The MACRO trial shows that endoscopic sinus surgery has clinical effectiveness in patients with chronic rhinosinusitis, providing significantly improved disease-specific quality of life at 6 months. Conversely, the trial findings do not support routine long-term use of low-dose clarithromycin. Endoscopic sinus surgery should be recommended if intranasal medication alone is unable to achieve symptom control. National Institute for Health and Care Research Programme Grants for Applied Research.