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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Esomeprazole 40mg | Drug | Nexium (esomeprazole), 40mg, bid, for 14 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Eradication rate by intention to treat analysis | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Eradication rate by per protocol analysis | 8 weeks | |
| frequency of adverse effects during eradication therapy | 2 weeks | |
| changes of fecal microbiota |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jyh-Ming Liou, MD, PhD | Contact | 886972651883 | jyhmingliou@gmail.com | |
| Mei-Jyh Chen, MD | Contact | 886223123456 | 63541 | migichen@ntuh.gov.tw |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jyh-Ming Liou | Recruiting | Taipei, Taiwan | Taiwan | 10002 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37178702 | Derived | 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. |
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| ID | Term |
|---|---|
| D064098 | Esomeprazole |
| D000658 | Amoxicillin |
| D008795 | Metronidazole |
| D064704 | Levofloxacin |
| D001729 | Bismuth |
| D013752 | Tetracycline |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
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| Amoxicillin | Drug | amoxicillin, 1000mg, bid, for 7 days (day 1-day 7) |
|
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| metronidazole | Drug | metronidazole, 500mg, bid, for 7 days (day 8-14) |
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| Levofloxacin 500mg | Drug | levofloxacin 250mg, bid, for 7 days (day 8-14) |
|
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| Clarithromycin ER | Drug | clarithromycin 500mg, bid, for 7 days (day 8-14) |
|
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| Esomeprazole 40mg | Drug | Nexium (esomeprazole), 40mg, bid, for 10 days |
|
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| Dibismuth trioxide | Drug | Dibismuth trioxide，KCB F.C. TABLETS，300mg，qid, for 10 days |
|
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| metronidazole | Drug | metronidazole, 500mg, tid, for 10 days (day 1-10) |
|
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| tetracycline | Drug | tetracycline 500mg, qid, for 10 days |
|
|
changes of fecal microbiota before and after erdication therapy |
| 1 year |
| reinfection rate | reinfection rate 1 year after eradication therapy | 1 year |
| Yu Jen Fang, MD | National Taiwan University Hospital, Yun-Lin Branch | Principal Investigator |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D015242 | Ofloxacin |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D004603 | Elements, Radioactive |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D019216 | Metals, Heavy |
| D011868 | Radioisotopes |
| D007554 | Isotopes |
| D008670 | Metals |
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |