Explore the vast range of titles available.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world’s population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13 C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti- H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori -negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti- H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74–0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69–0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 . A cluster-randomized trial carried out across 980 villages in a high-risk region in China found that systematic treatment of antibiotics, omeprazole and bismuth modestly reduced gastric cancer incidence in Helicobacter pylori -positive populations.

Background and aimsThis study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy.MethodsIn this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.Results300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI −4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI −4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI −2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).ConclusionsVT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.Trial registration numberChiCTR2300074693.

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.

Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae. IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated. Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively. Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens. NCT01844856.

Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative 13C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955. 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of −10% (95% CI 15·1–32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy. Axcan Pharma Inc.

BackgroundBismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori.MethodsTreatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication.ResultsThe per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups.ConclusionCompared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication. This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test. There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001). Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance. The Thai Clinical Trial Registry (TCTR) 20170623004.

Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection. Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment. The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003). Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

Background. Increasing rates of failure of artemisinin-based combination therapy have highlighted the possibility of emerging artemisinin resistance along the Thai-Cambodian border. We used an integrated in vivo-in vitro approach to assess the presence of artemisinin resistance in western Cambodia. This article provides additional data from a clinical trial that has been published in The New England Journal of Medicine. Methods. Ninety-four adult patients from Battambang Province, western Cambodia, who presented with uncomplicated falciparum malaria were randomized to receive high-dose artesunate therapy (4 mg/kg/day orally for 7 days) or quinine-tetracycline. Plasma concentrations of dihydroartemisinin, in vitro drug susceptibility, and molecular markers were analyzed. Cases meeting all the following criteria were classified as artemisinin resistant: failure to clear parasites within 7 days of treatment or reemergence of parasites within 28 days of follow-up; adequate plasma concentrations of dihydroartemisinin; prolonged parasite clearance; and increased in vitro drug susceptibility levels for dihydroartemisinin. Results. Two (3.3%) of 60 artesunate-treated patients were classified as artemisinin resistant. Their parasite clearance times were prolonged (133 and 95 h, compared with a median of 52.2 h in patients who were cured). These patients had 50% inhibitory concentrations of dihydroartemisinin that were almost 10 times higher than the reference clone W2. Resistance did not appear to be mediated by the pfmdr1 copy number or selected PfATPase6 polymorphisms previously proposed to confer artemisinin resistance. Conclusion. Artemisinin resistance has emerged along the Thai-Cambodian border. The potentially devastating implications of spreading resistance to a drug that currently has no successor call for further studies of this emerging problem. Clinical trial registration. ClinicalTrials.gov identifier NCT00479206.

Background Vonoprazan and amoxicillin dual therapy has demonstrated favorable efficacy in the initial treatment of Helicobacter pylori (H. pylori) infection. This study aimed to evaluate the efficacy and safety of vonoprazan and high‐dose amoxicillin (VHA) dual therapy for H. pylori rescue treatment. Methods This was an open label, multicenter, non‐inferiority, and randomized controlled clinical trial conducted at four institutions in both central and northwestern China. A total of 688 H. pylori‐infected patients who had failed previous treatments were randomly assigned (1:1) to receive either VHA dual therapy or the tetracycline‐ and furazolidone‐based bismuth‐containing quadruple therapy (TFEB) for 14 days. Eradication rates, adverse event (AE) rates, and the patient compliance were compared between the two groups. Results The eradication rates in the VHA and TFEB groups were 73.8% and 76.2% (p = 0.481), respectively, by intention‐to‐treat (ITT) analysis; 81.9% and 85.6% (p = 0.215), respectively, by modified ITT (MITT) analysis; and 82.1% and 85.6% (p = 0.248), respectively, by per‐protocol (PP) analysis. VHA therapy remained non‐inferior to TFEB in ITT, MITT, and PP analyses. The overall AE incidence in the VHA group was significantly lower compared with that in the TFEB group (13.4% vs.. 28.5%, p < 0.001). Patients' compliance was similar between the two groups. A history of multiple prior eradication failures was an independent risk factor (2 failures: OR = 0.566, p = 0.032; ≥ 3 failures: OR = 0.335, p < 0.001) reducing the efficacy of H. pylori rescue therapy. Conclusion The 14‐day VHA dual therapy was non‐inferior to bismuth‐containing quadruple therapy, with a lower incidence of adverse events and good compliance, and may represent an effective alternative for H.pylori rescue treatment. Trial Registration This trial was registered at ClinicalTrials.gov (No. NCT06168084) Summary Summarise the established knowledge on this subject ◦ VHA dual therapy demonstrated significant efficacy in first‐line H. pylori treatment. ◦ BQT remains the recommended rescue regimen in most guidelines. ◦ BQT may pose challenges such as higher adverse events and potential secondary resistance risk in H. pylori. What are the significant and/or new findings of this study? ◦ VHA dual therapy was non‐inferior to BQT and may represent an effective alternative for H. pylori rescue treatment. ◦ A history of multiple prior eradication failures was an independent risk factor reducing the efficacy of H. pylori rescue therapy.