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High Dose Amoxicillin Versus Tetracycline as Second-line Treatment of Resistant Helicobacter Pylori Infection

Phase 4
Completed
Conditions
Helicobacter Pylori Treatment Failure
Interventions
Registration Number
NCT02175927
Lead Sponsor
Shanghai Jiao Tong University School of Medicine
Brief Summary

No trial has examined the the efficacy of high dose amoxicillin based quadruple therapy as second-line treatment for Helicobacter pylori infection. The study aims to compare the effectiveness and safety of 14-day high dose amoxicillin-based quadruple regiment with classical quadruple regiment for rescue eradication of Helicobacter pylori.

Detailed Description

Helicobacter pylori is the most successful human pathogen infecting an estimated 50% of the global population, and is associated with a spectrum of disease states, including chronic gastritis, duodenal and gastric ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma (MALToma).

Most Consensus Conferences and Clinical Guidelines recommend the prescription of a triple therapy including a proton pump inhibitor (PPI) and clarithromycin with either amoxicillin or metronidazole, as first-line treatment. However, the effectiveness of these triple-therapy regimens seems to have diminished over time, largely as a result of emerging resistance of the organism to clarithromycin. Avoiding problems due to antibiotic resistance has become an important issue when deciding a second-line rescue therapy for H. pylori infection

Bismuth-containing quadruple therapies have been used widely in second-line therapy of H. pylori infection, and are recommended by the Maastricht IV Consensus Conference report. Quadruple therapy can achieve a high rate of eradication success as a second-line treatment. A meta-analysis of quadruple therapy showed that metronidazole resistance had limited effect on the outcome when adequate dosages and durations are used. This meta-analysis also showed that compliance with quadruple therapy is high. Classical bismuth-based quadruple therapy consists of a PPI, bismuth, tetracycline and metronidazole. This regiment meets the proposed criteria for a second-line treatment: it does not contain the key antibiotic of the original regimen (clarithromycin), the treatment is not affected by clarithromycin resistance, metronidazole resistance in vitro does not affect the outcome of quadruple therapy significantly, compliance with the regimen is high and the regimen is effective in most parts of the world. But this regiment has high rate of side effects because of tetracycline.

Amoxicillin has low resistance rate as well as low percentage of side effects. The replacement of tetracycline by high dose amoxicillin in classical bismuth-containing quadruple therapy may be a better choice. Therefore, we will do a randomized trial to compare the eradication rate of 14-day high dose amoxicillin and metronidazole based bismuth-containing quadruple therapy with classical quadruple therapy for second-line Helicobacter pylori treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
312
Inclusion Criteria
  • all patients had failed H.pylori therapies including clarithromycin, metronidazole and/or amoxicillin (if not allergic) before
  • indication of rescue H pylori eradication treatment
  • Ability and willingness to participate in the study and to sign and give informed consent
Exclusion Criteria
  • patients less than 18 years old
  • previous gastric surgery
  • pregnancy or lactation
  • major systemic diseases,
  • administration of antibiotics, bismuth, antisecretory drugs in the preceding 8 weeks
  • allergy to any one of the medication used in the quadruple regimens.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High Dose AmoxicillinBismuth Potassium CitrateHigh dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid
TetracyclineBismuth Potassium CitrateClassical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid
High Dose AmoxicillinMetronidazoleHigh dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid
High Dose AmoxicillinAmoxicillinHigh dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid
High Dose AmoxicillinLansoprazoleHigh dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid
TetracyclineLansoprazoleClassical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid
TetracyclineMetronidazoleClassical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid
TetracyclineTetracyclineClassical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid
Primary Outcome Measures
NameTimeMethod
Eradication rate of Helicobacter pylori2 months

Access eradication rate of H. pylori by intention to treat (ITT) and per-protocol (PP) analysis in each treatment group

Secondary Outcome Measures
NameTimeMethod
Frequency of side effects of each treatment2 months

Score side effects as mild, moderate or severe according to their influence on daily activities

Trial Locations

Locations (1)

Shanghai Renji Hospital, Shanghai Jiao-Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

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