Clinical trial NCT03555526: Genotypic Resistance Guided Therapy for Refractory H. Pylori Infection
Official title: Comparison of Genotypic Resistance Guided Versus Susceptibility Testing Guided Therapy for the Third-line Eradication of H. Pylori- a Multicenter Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: H Pylori Infection
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2018-06-13
Enrollment: 320
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Eradication rate by intention to treat analysis
timeFrame: 8 weeks
Secondary outcomes:
measure: Eradication rate by per protocol analysis
timeFrame: 8 weeks
measure: frequency of adverse effects during eradication therapy
timeFrame: 2 weeks
measure: changes of fecal microbiota
timeFrame: 1 year
measure: reinfection rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Taipei, Taiwan
country: Taiwan
facility: Jyh-Ming Liou
state: Taiwan-
Study officials:
affiliation: National Taiwan University Hospital (recruiting)
name: Jyh-Ming Liou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital Hsin-Chu Branch
name: Yen-Nien Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital, Yun-Lin Branch
name: Yu Jen Fang, MD
role: PRINCIPAL_INVESTIGATOR
References: