Amoxicillin/Metronidazole Based Quadruple Therapy for Helicobacter Pylori Eradication

Dyspepsia Clinical Trial

Official title:

Prospective, Randomized Controlled Trial Comparing Amoxicillin and Metronidazole Based Bismuth-containing Quadruple Therapy With Amoxicillin and Clarithromycin Based Quadruple Therapy for First-line Helicobacter Pylori Eradication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175901
• Other study ID #: rjkls2014006
• Status: Completed
• Phase: Phase 4
• First received: June 24, 2014
• Last updated: February 2, 2015
• Start date: July 2014
• Est. completion date: January 2015

Study information

• Verified date: February 2015
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

No trial has examined the the efficacy of amoxicillin and metronidazole based quadruple therapy for Helicobacter pylori treatment. The study aims to compare the effectiveness and safety of 14-day amoxicillin-/metronidazole-based quadruple regiment and classical quadruple regiment for Helicobacter pylori eradication.

Description:

Helicobacter pylori is the most successful human pathogen infecting an estimated 50% of the global population. It is a common and potentially curable cause of dyspepsia and peptic ulcer disease. Eradication in patients with peptic ulcer or even functional or non-investigated dyspepsia is a cost effective approach.

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. Due to the low efficacy achieved with these treatments, they have been deemed as unethical comparators in clinical trials. As antimicrobial resistance becomes more prevalent worldwide, treatment failure rates are likely to continue increasing, suggesting that new regimens for H pylori eradication must be sought.

Bismuth-containing quadruple therapies have been used widely in H. pylori therapy with many permutations of doses and durations and with variable results. Classical bismuth-based quadruple therapy containing a PPI, bismuth, tetracycline and metronidazole has been recommended as the first-line treatment by the Maastricht IV Consensus Conference report and H. pylori Study Group of Chinese Society of Gastroenterology. But this regiment has high rate of side effects because of tetracycline. Standard triple therapy-based, bismuth-containing quadruple Therapy is also an alternative. Though addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin, its use as a first-line treatment is limited in areas of high clarithromycin resistance.

Amoxicillin has low resistance rate as well as low percentage of side effects. The combination of amoxicillin and metronidazole in bismuth-containing quadruple therapy may be a better choice, which can avoid clarithromycin resistance and reduce side effects. Therefore, we will do a randomized trial to compare the eradication rate of 14-day amoxicillin and metronidazole based bismuth-containing quadruple therapy with amoxicillin and clarithromycin based quadruple therapy for Helicobacter pylori infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participants with non-investigated/functional dyspepsia or scarred peptic ulcer with indication of H pylori eradication treatment

• Ability and willingness to participate in the study and to sign and give informed consent

• confirmed H pylori infection by at least one of the following methods: C13-urea breath test, histology, rapid urease test or bacterial culture.

Exclusion Criteria:

• patients with peptic ulcer

• previous H. pylori eradication therapy

• Age below 18 years

• major systemic diseases

• previous gastric surgery

• pregnancy or breastfeeding

• allergy to any of the study drugs

• receipt of anti-secretory therapy, antibiotics or bismuth salts 4 weeks prior to inclusion

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyspepsia
• Peptic Ulcer

Intervention

Drug:
• Lansoprazole
antisecretory drug of each quadruple therapy
• Bismuth Potassium Citrate
one component of each quadruple therapy
• Amoxicillin
antibiotic of each quadruple therapy
• Metronidazole
antibiotic of the amoxicillin/metronidazole-based quadruple therapy
• Clarithromycin
antibiotic of the amoxicillin/clarithromycin-based 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 (3)

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

Sun Q, Liang X, Zheng Q, Liu W, Xiao S, Gu W, Lu H. High efficacy of 14-day triple therapy-based, bismuth-containing quadruple therapy for initial Helicobacter pylori eradication. Helicobacter. 2010 Jun;15(3):233-8. doi: 10.1111/j.1523-5378.2010.00758.x. — 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, clarithromycin, and metronidazole by the twofold agar dilution method.	2 months	No
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	No
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	Yes