Sequential therapy for 10?days versus triple therapy for 14?days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial.
ABSTRACT: OBJECTIVE:Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10?days (S10) versus triple therapy for 14?days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. DESIGN:We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5?days, followed by lansoprazole, clarithromycin and metronidazole for another 5?days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14?days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6?weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS:The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. CONCLUSIONS:S10 was not superior to T14 in areas with low clarithromycin resistance. TRIAL REGISTRATION NUMBER:NCT01607918.
Project description:Background:Whether adjunctive N-acetylcysteine (NAC) may improve the efficacy of triple therapy in the first-line treatment of Helicobacter pylori infection remains unknown. Our aim was to compare the efficacy of 14-day triple therapy with or without NAC for the first-line treatment of H. pylori. Material and methods:Between 1 January 2014 and 30 June 2018, 680 patients with H. pylori infection naïve to treatment were enrolled in this multicenter, open-label, randomized trial. Patients were randomly assigned to receive triple therapy with NAC [NAC-T14, dexlansoprazole 60?mg four times daily (q.d.); amoxicillin 1?g twice daily (b.i.d.), clarithromycin 500?mg b.i.d., NAC 600?mg b.i.d.] for 14?days, or triple therapy alone (T14, dexlansoprazole 60?mg q.d.; amoxicillin 1?g b.i.d., clarithromycin 500?mg b.i.d.) for 14?days. Our primary outcome was the eradication rates by intention to treat (ITT). Antibiotic resistance and CYP2C19 gene polymorphism were determined. Results:The ITT analysis demonstrated H. pylori eradication rates in NAC-T14 and T14 were 81.7% [276/338, 95% confidence interval (CI): 77.5-85.8%] and 84.3% (285/338, 95% CI 80.4-88.2%), respectively. In 646 participants who adhered to their assigned therapy, the eradication rates were 85.7% and 88.0% with NAC-T14 and T14 therapies, respectively. There were no differences in compliance or adverse effects. The eradication rates in subjects with clarithromycin-resistant, amoxicillin-resistant, or either clarithromycin/amoxicillin resistant strains were 45.2%, 57.9%, and 52.2%, respectively, for NAC-T14, and were 66.7%, 76.9%, and 70.0%, respectively, for T14. The efficacy of NAC-T14 and T14 was not affected by CYP2C19 polymorphism. Conclusion:Add-on NAC to triple therapy was not superior to triple therapy alone for first-line H. pylori eradication [ClinicalTrials.gov identifier: NCT02249546].
Project description:Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437.1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites.Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations.Bill & Melinda Gates Foundation, US National Institutes of Health.
Project description:Ten-day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90-94% (Grade B success).We tested whether prolonging treatment and continuing amoxicillin throughout the 14-day treatment period would produce a ? 95% result.This was a multicenter pilot study in which H. pylori-infected patients received a 14-day sequential-concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ? 95% eradication by per-protocol analysis.One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3-100.0%) by per-protocol analysis and 97.4% by intention-to-treat analysis (95% CI, 94.5-100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%.Fourteen-day hybrid sequential-concomitant therapy achieved > 95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.
Project description:Eradication of helicobacter pylori is important for treatment of GU but an ideal regimen is not available. HP is resistant to metronidazole and clarithromycin. Clarithromycin is expensive and is not available in under developing countries. This study aimed to compare two regimens containing clarithromycin or azithromycin.Totally, seventy-eight patients with GU (confirmed with endoscopy) and infection of HP (Confirmed by Rapid Urease Test (RUT)) were allocated to one of the groups of study (35 participants in each group). Two weeks regimen of Clarithromycin (2×500 mg) + Amoxicillin (2×1 gr) + omeprazole (2×20 mg) was administered for group A of patients while group B got a 10 days regimen of Azithromycin (1×250 mg) + 14 days Amoxicillin (2×1 gr) + omeprazole (2×20 mg). At the end of the treatment course, the patients were evaluated according to the side effects of the drugs. In addition, two months after the end of therapy, patients underwent endoscopy and biopsy to evaluate HP eradication.After two weeks, the side effects of the drug were: Nausea 8 patients in group A and 7 patients in group B, Diarrhea 2 patients in group A, 3 patients in group B and vomiting 2 patients in group A, 3 patients in group B. There were no serious side effects in any group. Eradication rate in group A was 82.9% (based on per protocol analysis (PPA)) and 84.6 % (intention to treat (ITT)). In group B, eradication rate was 77.1 % (PPA) and 79.5 % (ITT) (P=0.55).Based on our study results, azithromycin can be used in HP eradication regimen because of its similar efficacy to clarithromycin but also have lower cost, side effects and resistance.
Project description:Context:Goals: To compare the efficacy of standard triple therapy with clarithromycin versus triple therapy with levofloxacin for treatment of Helicobacter pylori-positive infection in a referral hospital in Damascus, Syria. Design:pilot prospective open-label randomized controlled trial. Subjects and Methods:Eighty treatment-naive patients who tested positive for H. pylori gastric infection were randomly assigned to one of two treatment groups with randomization ratio of 50/50. Group (A) was treated with clarithromycin (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg), each twice/day for 14 days, while Group (B) was treated with levofloxacin (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg), each twice/day for 14 days. After 6 weeks of treatment, all patients underwent endoscopy and biopsy to evaluate H. pylori infection eradication. Results:Forty patients were allocated in each group; 37 patients completed the follow-up in each group. Thirteen patients in Group (A) were cured, with an eradication rate of 35.1% according to per-protocol analysis (PPA) and 32.5% according to intention-to-treat analysis (ITT), while in Group (B), 11 patients were cured, with an eradication rate of 29.7% according to PPA and 27.5% according to ITT with P = 0.80. No serious adverse events reported in both the groups. Conclusions:Clarithromycin is slightly better than levofloxacin in treatment of H. pylori gastric infection, but both regimens show low effectiveness with suboptimal eradication rates in our selected population.
Project description:BACKGROUND/AIMS:Clarithromycin resistance in Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the point mutations. METHODS:A total of 431 adult patients with H. pylori infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for seven days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for seven days. H. pylori eradication rates were compared. RESULTS:Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C). The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The overall H. pylori eradication rate was 83.7%, and the seven-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the seven-day PAC-treated nonresistance group (ITT; 55.4% (51/92) vs. 74.3% (252/339), p = 0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), p = 0.0001). CONCLUSIONS:There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori when treated with PAM for seven days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.
Project description:OBJECTIVE:The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. DESIGN:A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20?mg to lansoprazole 30?mg as part of first-line triple therapy (with amoxicillin 750?mg and clarithromycin 200 or 400?mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750?mg and metronidazole 250?mg) as an open-label treatment. RESULTS:Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. CONCLUSION:Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. TRIAL REGISTRATION NUMBER:NCT01505127.
Project description:Background:After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. Methods:Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. Results:From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n?=?182) than in the LBQT group (n?=?182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P?<?0.001) and per protocol (PP) analysis (91.1% vs. 67.8%, P?<?0.001). Among patients in the TBQT group with levofloxacin susceptibility, eradication rates were similar in the ALEB (n?=?51) and AFEB (n?=?50) subgroups according to both the ITT (86.3% vs. 90.0%, P?=?0.56) and PP (88.0% vs. 90.0%, P?=?0.75) analyses. Isolated clarithromycin and levofloxacin resistance rates were 57.7% and 44.5%, respectively. The total clarithromycin and levofloxacin resistance rate in strains with dual or triple resistance was 35.7%. Conclusions:TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance.Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR1900027743.
Project description:The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy.In total, 390?H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication.Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P?=?0.240 and P?=?0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P?=?0.040).Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy.ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
Project description:The efficacy and applicability of molecular testing to guide the selection of antibiotics in triple Helicobacter pylori (H. pylori) eradication regimens have not been reported. We tested a 7-day, genotypic resistance-guided triple H. pylori eradication therapy in a high-resistance setting.Consecutive dyspeptic patients with H. pylori infection were prospectively enrolled. Genotypic resistances to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) were determined from gastric biopsy specimens using a commercially available molecular assay (GenoTypeâ HelicoDR). A tailored genotypic resistance-guided 7-day triple therapy comprised esomeprazole, amoxicillin, and either clarithromycin (wild-type 23SrRNA), levofloxacin (23SrRNA mutated/wild-type gyrA) or rifabutin (both 23SrRNA/gyrA mutated). H. pylori eradication was confirmed by 13C-urea breath test.Of 148 subjects screened, 51 patients were enrolled (male/female: 27/24, mean age: 50.7±11.4 years, treatment-naïve/-experienced: 32/19). The molecular kit was easily implemented, allowing for rapid (within 24 h) and relatively inexpensive determination of H. pylori resistance (clarithromycin: 47.1%, fluoroquinolones: 15.7%, dual clarithromycin/fluoroquinolones: 7.8%). For patients who received clarithromycin-, levofloxacin- and rifabutin-containing triple therapy, the respective eradication rates were 24/27, 20/20, and 2/4 by intention-to-treat (ITT); and 24/24, 19/19 and 2/3 by per-protocol (PP) analysis. Overall eradication rates were 90.2% (95% confidence interval [CI] 77.8-96.3%) by ITT and 97.8% (95%CI 87-99.8%) by PP analysis, showing no significant difference between treatment-naïve and -experienced patients (ITT: 87.5% vs. 94.7%, P=0.64; PP: 96.4% vs. 100%, respectively, P=1.00).Regardless of prior treatment history, a genotypic resistance-guided 7-day triple therapy, based on a simple molecular assay, achieved a high H. pylori eradication rate.