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

Helicobacter Pylori Treatment Failure Clinical Trial

Official title:

Prospective, Randomized Controlled Trial Comparing High Dose Amoxicillin Versus Tetracycline Based Quadruple Therapy as Second-line Treatment for Resistant Helicobacter Pylori Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175927
• Other study ID #: rjkls2014007
• Status: Completed
• Phase: Phase 4
• First received: June 24, 2014
• Last updated: February 29, 2016
• Start date: July 2014
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Helicobacter Infections
• Helicobacter Pylori Treatment Failure

Intervention

Drug:
• Lansoprazole
antisecretory drug of each quadruple therapy
• Bismuth Potassium Citrate
one component of each quadruple therapy
• Metronidazole
antibiotic of each quadruple therapy
• Amoxicillin
antibiotic of high dose amoxicillin based quadruple therapy
• Tetracycline
antibiotic of classical quadruple therapy

Locations

Country	Name	City	State
China	Shanghai Renji Hospital, Shanghai Jiao-Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (2)

Lu H, Zhang W, Graham DY. Bismuth-containing quadruple therapy for Helicobacter pylori: lessons from China. Eur J Gastroenterol Hepatol. 2013 Oct;25(10):1134-40. doi: 10.1097/MEG.0b013e3283633b57. Review. — View Citation

Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012 May;61(5):646-64. doi: 10.1136/gutjnl-2012-302084. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimal inhibitory concentrations (MIC) of antibiotics against each helicobacter pylori clinical isolate	Determine MIC of amoxicillin, tetracycline, and metronidazole by the twofold agar dilution method.	2 months
Primary	Eradication rate of Helicobacter pylori	Access eradication rate of H. pylori by intention to treat (ITT) and per-protocol (PP) analysis in each treatment group	2 months
Secondary	Frequency of side effects of each treatment	Score side effects as mild, moderate or severe according to their influence on daily activities	2 months