Clinical trial NCT02175927: High Dose Amoxicillin Versus Tetracycline as Second-line Treatment of Resistant Helicobacter Pylori Infection
Official title: Prospective, Randomized Controlled Trial Comparing High Dose Amoxicillin Versus Tetracycline Based Quadruple Therapy as Second-line Treatment for Resistant Helicobacter Pylori Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Helicobacter Pylori Treatment Failure
Keywords: Helicobacter pylori
Treatment Failure
second-line therapy
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2014-06-26
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Eradication rate of Helicobacter pylori
timeFrame: 2 months
Secondary outcomes:
measure: Frequency of side effects of each treatment
timeFrame: 2 months
Other outcomes:
measure: Minimal inhibitory concentrations (MIC) of antibiotics against each helicobacter pylori clinical isolate
timeFrame: 2 months
Locations:
city: Shanghai
country: China
facility: Shanghai Renji Hospital, Shanghai Jiao-Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Hong Lu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.