Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area.

BACKGROUND: Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations. MATERIALS AND METHODS: This multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by (13)C-urea breath test or histology 4-6weeks after treatment. Adverse events and adherence were evaluated. RESULTS: Allocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7-18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6-17.6). Overall, adherence was (98.9%, 95% CI=97-100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5-33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment. CONCLUSIONS: Concomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.

Clinical evaluation of a ten-day regimen with esomeprazole, metronidazole, amoxicillin, and clarithromycin for the eradication of Helicobacter pylori in a high clarithromycin resistance area.

BACKGROUND: Increasing clarithromycin resistance reduces Helicobacter pylori eradication rates with conventional triple regimens. We evaluated effectiveness and safety of a 10-day-quadruple nonbismuth containing regimen, as first-line treatment or second-line treatment (after conventional triple) for H. pylori, and assessed impact of antibiotic resistance on treatment success. MATERIALS AND METHODS: Eligible patients had upper GI endoscopy and positive CLO-test, also confirmed by histology and/or culture. The eradication scheme comprised: Esomeprazole 40 mg, Metronidazole 500 mg, Amoxicillin 1000 mg, and Clarithromycin 500 mg, twice daily, for 10 days. Treatment adherence and adverse effects were recorded. Eradication was tested by (13) C-urea breath test or histology. RESULTS: One hundred and ninety out of 198 patients (115M/83F, aged 18-81, mean 52 years, 37% smokers, 27% ulcer disease) who completed the study protocol were evaluated for eradication. Adherence to treatment was 97.7% (95% CI 95.9-99.6). Six (3.2%) patients experienced severe side effects and discontinued treatment. Intention to treat and per protocol analysis in first line was 91.5% (95% CI 86.2-94.8) and 95% (95% CI 90.4-97.4) and in second line was 60.6% (95% CI 43.6-75.3) and 64.5% (95% CI 46.9-78.8), respectively. Antibiotic susceptibility tests were performed in 106 of 124 (85%) patients who gave consent. Among them 42 (40%) harbored clarithromycin resistant strains. Eradication rates were significantly higher in sensitive and single clarithromycin or metronidazole resistant (37/37, 100% and 43/47, 91%) than in dual resistant strains (12/22, 55%) (p < .0001). Specifically, concomitant regimen eradicated 7/10, 70% of dual resistant strains as first-line treatment and 5/12, 42% as second-line treatment. Multivariate analysis showed that dual resistance was the only independent significant predictor of treatment failure. CONCLUSIONS: The 10-days "concomitant" regimen is effective and safe first-line H. pylori treatment, in a high clarithromycin resistance area, although dual antibiotic resistance may compromise its effectiveness.

Screening for gastric premalignant lesions with narrow band imaging, white light and updated Sydney protocol or both?

BACKGROUND: Narrow band imaging (NBI) can accurately discriminate gastritis but premalignant lesions (PMLs) are difficult to detect. AIMS: The purpose of this study was to compare white light endoscopy (WLE) and histopathologic findings using the updated Sydney protocol (USP) with NBI and targeted biopsies (TB). METHODS: One hundred nineteen symptomatic patients referred for upper GI endoscopy were included in this prospective open study. All patients were assessed for gastritis and PMLs using WLE and NBI by two endoscopists selected in a random manner. Biopsies were taken according to USP and targeted from any area suspicious for PML. Imaging and histological findings between protocols were compared. RESULTS: In total 45 patients (38 %) had atrophy of whom 39 (32.7 %) were detected with WLE-USP and 28 (23.5 %) with NBI-TB (p = 0.03), 25 (21 %) had intestinal metaplasia (IM) of whom 19 (16 %) were detected with WLE-USP and 18 (15.1 %) with NBI-TB (p = 0.7) and 14 (12 %) had dysplasia of whom 12 (10 %) were detected with WLE-USP and 7 (7 %) with NBI-TB (p = 0.5), and 1 (0.8 %) case of gastric cancer only detected with WLE-USP. Accuracies for atrophy and IM were 93 and 90 % for the WLE-USP and 80 and 82 % for NBI-TB. The NBI-TB detected six cases of atrophy (13 %), 5 (20 %) of IM, and 2 (14 %) of dysplasia missed by WLE-USP as agreement was moderate. Accuracies of the NBI patterns for body and antral gastritis were 80 and 84 %. CONCLUSIONS: In a non high-risk population NBI-TB has less accuracy in detecting premalignant lesions compared to WLE-USP. However, it may be used as an important and easy-to-use complementary method which increases overall detectability for gastric premalignant lesions.