Clinical trial NCT02175901: Amoxicillin/Metronidazole Based Quadruple Therapy for Helicobacter Pylori Eradication
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dyspepsia
Peptic Ulcer
Keywords: helicobacter pylori eradication
antibiotic
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2014-06-26
Enrollment: 215
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 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.

Detailed 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.

Eligibility criteria: 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

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: 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.
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.
citation: Zhang W, Chen Q, Liang X, Liu W, Xiao S, Graham DY, Lu H. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy. Gut. 2015 Nov;64(11):1715-20. doi: 10.1136/gutjnl-2015-309900. Epub 2015 Sep 2.