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Genotypic Resistance Guided Versus Susceptibility Testing Guided Therapy for the First-line Eradication of H. Pylori

Phase 4
Conditions
Helicobacter Pylori Infection
Interventions
Drug: SGT
Drug: GGT
Registration Number
NCT03556254
Lead Sponsor
National Taiwan University Hospital
Brief Summary

We aimed to (1) compare the efficacy of genotypic resistance guided sequential therapy vs. susceptibility testing guided therapy in the first-line therapy (2) assess the long term impact of eradication therapy on the antibiotic resistance and microbiota of the gut flora and the metabolic factors in this multi-center, open labeled trial

Detailed Description

Background: Recent trials have shown that susceptibility testing guided therapy was more effective than empirical triple therapy given for 7-10 days in the first-line treatment of H. pylori infection. However, susceptibility testing is time consuming and inconvenient, limiting the widespread application of susceptibility testing guided therapy in clinical practice. Recently, point mutations at 23S rRNA and gyrase A have reported to be associated with clarithromycin and levofloxacin resistance. However, whether genotypic resistance guided therapy is more effective or non-inferior to susceptibility guided therapy has not been reported. Besides, the long term impact of H. pylori eradication on the gut microbiota and metabolic disorders remains unclear. Aim: Therefore, we aimed to (1) compare the efficacy of genotypic resistance guided sequential therapy vs. susceptibility testing guided therapy in the first-line therapy(2) assess the long term impact of eradication therapy on the antibiotic resistance and microbiota of the gut flora and the metabolic factorsMethods: This will be a multi-center, open labeled trialPatients: 560 patients with H. pylori infection naïve to eradication therapy will be enrolled Testing for H. pylori infectionBefore First Line TreatmentAny two positive of CLO test, histology, HpSA, and culture will be considered as H. pylori infectedAfter First-Line Treatment: C13-UBT will be used to assess the existence of H. pylori 6-8 weeks after first line therapy. Long term reinfection: C13-UBT will be used to assess the recurrence of H. pylori 1 year after eradication therapy Determination of antibiotic resistance of H. pylori: E-test will be used to determine the minimum inhibitory concentrations of clarithromycin and levofloxacin to guide the selection of antibiotics. Agar dilution test will also be done. Mutations in 23S rRNA and gyrase A will also be determined by PCR followed by direct sequencing Treatment regimens and assignment Eligible patients will be randomized to receive either one of the treatments (A) Genotypic resistance guided therapy: In the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given. (B) Susceptibility testing guided therapy: In the absence of clarithromycin resistance, clarithromycin based sequential therapy will be given. In the presence of clarithromycin resistance but the absence of levofloxacin resistance, levofloxacin based sequential therapy will be given. In the presence of both clarithromycin and levofloxacin resistance or if culture fails, bismuth quadruple therapy will be given. 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 floraThe body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will be collected before and 8 weeks and 1 year after eradication therapy.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
560
Inclusion Criteria
  • Adult patients aged greater than 20 years with H. pylori infection naïve to treatment are considered eligible for enrollment..
Exclusion Criteria
  • children and teenagers aged less than 20 years
  • history of gastrectomy
  • gastric malignancy, including adenocarcinoma and lymphoma
  • previous allergic reaction to antibiotics (amoxicillin, clarithromycin, levofloxacin, metronidazole, bismuth) and prompt pump inhibitors (esomeprazole)
  • contraindication to treatment drugs
  • pregnant or lactating women
  • severe concurrent disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Susceptibility testing guided therapySGTTailored therapy according to the minimum inhibitory concentration result (susceptibility testing, E-test)
Genotypic resistance guided therapyGGTIn the absence of 23S rRNA mutation, clarithromycin based sequential therapy will be given. In the presence of 23S rRAN mutation but the absence of gyrase A mutation, levofloxacin based sequential therapy will be given. In the presence of both 23S rRNA and gyrase A mutations or if genotyping fails, bismuth quadruple therapy will be given.
Primary Outcome Measures
NameTimeMethod
Eradication rate will be evaluated according to Intent-to-treat (ITT) analyses6 weeks

Urea breath testing will be done at least 6 weeks after completion of eradication therapy

Secondary Outcome Measures
NameTimeMethod
adverse effects during eradication therapies2 weeks

a standard interview will be arranged at the end of treatment to assess the adverse effects

Trial Locations

Locations (1)

National Taiwan University Hospital, Yun-Lin Branch

🇨🇳

Yun-Lin County, Taiwan

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