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

Shanghai Jiao Tong University School of Medicine

Status and phase

Completed

Phase 4

Conditions

Helicobacter Pylori Treatment Failure

Treatments

Drug: Amoxicillin

Drug: Tetracycline

Drug: Metronidazole

Drug: Bismuth Potassium Citrate

Drug: Lansoprazole

Study type

Interventional

Funder types

Other

Identifiers

NCT02175927

rjkls2014007

Details and patient eligibility

About

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.

Full 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.

Enrollment

312 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

312 participants in 2 patient groups

High Dose Amoxicillin

Experimental group

Description:

High dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid

Treatment:

Drug: Bismuth Potassium Citrate

Drug: Lansoprazole

Drug: Metronidazole

Drug: Amoxicillin

Tetracycline

Active Comparator group

Description:

Classical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid

Treatment:

Drug: Bismuth Potassium Citrate

Drug: Lansoprazole