Genotypic Resistance Guided Therapy for Refractory H. Pylori Infection

NCT03555526 | Unknown Phase 4

• 1 other identifier: 201706037MINC
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

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.

Conditions

H Pylori Infection

Outcome Measures

Primary Outcomes (1)

• Eradication rate by intention to treat analysis

  8 weeks

Secondary Outcomes (4)

• Eradication rate by per protocol analysis

  8 weeks

• frequency of adverse effects during eradication therapy

  2 weeks

• changes of fecal microbiota

  1 year

• reinfection rate

  1 year

Study Arms (2)

Genotypic resistance guided therapy

EXPERIMENTAL

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.

Drug: Esomeprazole 40mg; Drug: Amoxicillin; Drug: metronidazole; Drug: Levofloxacin 500mg; Drug: Clarithromycin ER; Drug: Dibismuth trioxide; Drug: tetracycline

Phenotypic resistance guided therapy

ACTIVE COMPARATOR

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.

Drug: Esomeprazole 40mg; Drug: Amoxicillin; Drug: metronidazole; Drug: Levofloxacin 500mg; Drug: Clarithromycin ER; Drug: Dibismuth trioxide; Drug: tetracycline

Interventions

Esomeprazole 40mg DRUG

Nexium (esomeprazole), 40mg, bid, for 14 days

Also known as: Nexium (Sequential)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

Amoxicillin DRUG

amoxicillin, 1000mg, bid, for 7 days (day 1-day 7)

Also known as: Amoxicillin (Sequential)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

metronidazole DRUG

metronidazole, 500mg, bid, for 7 days (day 8-14)

Also known as: Flagyl (sequential)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

Levofloxacin 500mg DRUG

levofloxacin 250mg, bid, for 7 days (day 8-14)

Also known as: Cravit (sequential)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

Clarithromycin ER DRUG

clarithromycin 500mg, bid, for 7 days (day 8-14)

Also known as: Klaricid ER 500 (sequential)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

Dibismuth trioxide DRUG

Dibismuth trioxide，KCB F.C. TABLETS，300mg，qid, for 10 days

Also known as: KCB F.C., bismuth

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

tetracycline DRUG

tetracycline 500mg, qid, for 10 days

Also known as: tetracycline (bismuth quadruple therapy)

Genotypic resistance guided therapy; Phenotypic resistance guided therapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Jyh-Ming Liou

Taipei, Taiwan, Taiwan, 10002, Taiwan

RECRUITING

Related Publications (1)

• Chen MJ, Chen PY, Fang YJ, Bair MJ, Chen CC, Chen CC, Yang TH, Lee JY, Yu CC, Kuo CC, Chiu MC, Chou CK, Chen CY, Hu WH, Tsai MH, Hsu YC, Shun CT, Luo JC, Lin JT, El-Omar EM, Wu MS, Liou JM; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: two multicentre, open-label, randomised controlled, non-inferiority trials. Lancet Gastroenterol Hepatol. 2023 Jul;8(7):623-634. doi: 10.1016/S2468-1253(23)00097-3. Epub 2023 May 10.

  PMID: 37178702 DERIVED

MeSH Terms

Interventions

Esomeprazole; Amoxicillin; Metronidazole; Levofloxacin; Bismuth; Tetracycline

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Radioisotopes; Isotopes; Metals; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Jyh-Ming Liou, MD, PhD

  National Taiwan University Hospital (recruiting)

  PRINCIPAL INVESTIGATOR

• Yen-Nien Chen, MD

  National Taiwan University Hospital Hsin-Chu Branch

  PRINCIPAL INVESTIGATOR

• Yu Jen Fang, MD

  National Taiwan University Hospital, Yun-Lin Branch

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jyh-Ming Liou, MD, PhD

CONTACT

886972651883; jyhmingliou@gmail.com

Mei-Jyh Chen, MD

CONTACT

886223123456; migichen@ntuh.gov.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: June 13, 2018
• Study Start: December 15, 2017
• Primary Completion: September 1, 2021
• Study Completion: December 31, 2021
• Last Updated: June 13, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)