Genotypic Resistance Guided Therapy for Refractory H. Pylori Infection

National Taiwan University

Status and phase

Unknown

Phase 4

Conditions

H Pylori Infection

Treatments

Drug: Amoxicillin

Drug: Levofloxacin 500mg

Drug: Dibismuth trioxide

Drug: tetracycline

Drug: Esomeprazole 40mg

Drug: Clarithromycin ER

Drug: metronidazole

Study type

Interventional

Funder types

Other

Identifiers

NCT03555526

201706037MINC

Details and patient eligibility

About

The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.

Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.

Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.

Full description

The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.

Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.

Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy. Eradication status will be determined by 13C-urea breath test at least 6 weeks after eradication therapy. The stool samples will be collected before, and 2 and 8 weeks and 1 year after eradication therapy to analyze the changes in the antibiotic resistance and microbiota of gut flora. The body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will also be collected before and 2 weeks, 8 weeks and 1 year after eradication therapy.

Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.

Secondary End Points: the eradication rate according per protocol analysis and the adverse effects

Secondary End Point:

(A) Eradication rate according to per protocol analysis (PP analysis) (B) Frequency of adverse effects (C) The changes in the gut microbiota, antibiotic resistance of the Enterobacteriae, metabolic parameters before and after H. pylori eradication (D) The long term eradication rate and reinfection rate

Enrollment

320 estimated patients

Sex

All

Ages

20+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

H pylori infection failed after at least two eradication therapies
aged 20 years or greater
willingness to receive rescue therapy

Exclusion criteria

aged less than 20 years
history of gastric resection surgery
history of allergy to study drugs
pregnancy or lactating women
severe underlying illness, such as end stage renal disease, decompensated liver cirrhosis, or non-curative malignancy

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

320 participants in 2 patient groups

Genotypic resistance guided therapy

Experimental group

Description:

The regimen will be chosen according to the genotyping of 23S rRNA and gyrase A of H. pylori. In the absence of gyrase A mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of gyrase A mutation but in the absence of 23S rRNA mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both gyrase A and 23S rRNA mutation, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given.

Treatment:

Drug: metronidazole

Drug: Clarithromycin ER

Drug: Esomeprazole 40mg

Drug: tetracycline

Drug: metronidazole

Drug: Dibismuth trioxide

Drug: Esomeprazole 40mg

Drug: Levofloxacin 500mg

Drug: Amoxicillin

Phenotypic resistance guided therapy

Active Comparator group

Description:

The regimen will be chosen according to the susceptibility testing result. In the absence of levofloxacin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of levofloxacin resistance but in the absence of clarithromycin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both levofloxacin and clarithromycin resistance, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given.

Treatment:

Drug: metronidazole

Drug: Clarithromycin ER

Drug: Esomeprazole 40mg

Drug: tetracycline

Drug: metronidazole

Drug: Dibismuth trioxide

Drug: Esomeprazole 40mg

Drug: Levofloxacin 500mg

Drug: Amoxicillin