Drug Resistance, Multiple, Helicobacter Pylori
Conditions
Keywords
bismuth, microbial sensitivity tests, Helicobacter pylori, drug resistance, multiple
Brief summary
The goal of this clinical trial is to learn if the 14-day susceptibility-guided bismuth quadruple therapy works to treat multiple drug resistant Helicobacter pylori (H. pylori) in adults. It will also learn about the adverse effects of bismuth quadruple therapy. The main questions it aims to answer are: * Does 14-day susceptibility-guided bismuth quadruple therapy higher the eradication rate? * What medical problems do participants have when taking 14-day susceptibility-guided bismuth quadruple? Researchers will record 14-day susceptibility-guided bismuth quadruple to see if 14-day susceptibility-guided bismuth quadruple works to treat multiple drug resistant H. pylori. Participants will: * Take susceptibility-guided bismuth quadruple every day for 14 days * Visit the clinic once 4-6 weeks for checkups and tests * Keep a diary of their symptoms during taking susceptibility-guided bismuth quadruple
Detailed description
Helicobacter pylori (H. pylori) infection is the major culprit of dyspeptic symptoms, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The antibiotic resistance of H. pylori infection is an emerging issue. Moreover, amoxicillin-resistant H. pylori strains increased recently. The amoxicillin resistance rates were 9% in Asia and up to 39% in South America. Susceptibility-guided therapy is superior to empiric therapy in 2nd-line therapy. After twice eradication failure, H. pylori culture for susceptibility test is strongly recommended, which guide clinician to choose appropriate susceptibility-based therapy. The multiple drug resistant rates may be higher in patients who fail two or more eradication therapy; thus, susceptibility-guided therapy is currently the consensus recommendation for 3rd-line H. pylori eradication. Bismuth quadruple therapy could overcome either clarithromycin or metronidazole resistant strains. Several evidences of clinical randomized-controlled trials demonstrated that adding bismuth as the first line therapeutic regimen can capture additional 30%-40% successful eradication rate for the resistant strain, further contributing to the overall eradication rate. Accordingly, the aim of our study was to validate the susceptibility-guided bismuth quadruple therapy in patients with multiple drug resistant H. pylori infection in terms of efficacy and side effects.
Interventions
The investigators design four regimes for H. pylori eradication and participants receive one of the regimens based on susceptibility test. The four regimens are PBAT for those with both amoxicillin and tetracycline susceptible H. pylori; PBAM for those with amoxicillin susceptible but tetracycline resistant H. pylori; PBMT for those with amoxicillin resistant but tetracycline susceptible H. pylori; PBMR for those with both amoxicillin and tetracycline resistant H. pylori. A is amoxicillin (1000 mg thrice daily), B is colloidal bismuth subcitrate (120 mg thrice daily), M is metronidazole (500 mg thrice daily), P is a proton pump inhibitor, i.e., esomeprazole (40 mg twice daily), R is rifabutin (150 mg twice daily), and T is tetracycline (500 mg thrice daily). The treatment duration is 14 days for all regimens.
Sponsors
Ministry of Health and Welfare, Taiwan
National Cheng-Kung University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* H. pylori-infected with treatment experience with at least one course of eradication failure * H. pylori-infected with treatment naïve but having multiple-drug resistant H. pylori (\>= three antibiotics) * H. pylori infection confirmed by H. pylori culture
Exclusion criteria
* Previous allergic reactions to regimens, including amoxicillin, bismuth subcitrate, esomeprazole, metronidazole, rifabutin, and tetracycline, * Severe comorbidities, * Chronic kidney disease with estimated glomerular filtration rate \< 60 ml/min/1.73 m2, * Pregnant or breastfeeding women. * Dual-resistant H. pylori infection * Mono-resistant H. pylori infection * All susceptible H. pylori infection * Positive RUT but negative H. pylori culture * Negative RUT and negative H. pylori culture * Decline to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The eradication rate of H. pylori | From enrollment to the end of treatment at 6-8 weeks | The investigators define successful eradication as a negative 13C-urea breath test or a negative H. pylori stool antigen test at 4 to 6 weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by intention-to-treat and per-protocol analyses. The intention-to-treat analysis evaluates all enrolled participants. The per-protocol analysis evaluates those who take \>= 80% of the study medications and receive post-treatment 13C-urea breath test or an H. pylori stool antigen test. The successful rate is represented with a percentage (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse effects | From enrollment to the end of treatment at 2 weeks | Adverse events are assessed by a physician and a format questionnaire survey after the end of treatment. Serious adverse events are defined as daily activities restricted or participant unable to work. The adverse events include dizziness, skin rash, headache, unpleasant taste/bitter, abdominal pain, nausea, vomiting, diarrhea, constipation, abdominal fullness, glossitis/sore throat, darkened stool, fatigue, anorexia, chest burn, palpitation, and vaginal discharge. All adverse events are classified as none, mild (not restricting daily activities), or serious (restricting daily activities or causing inability to work). |
| Adherence to medications | From enrollment to the end of treatment at 2 weeks | Adherence to medications is evaluated by questionnaire surveys after treatment completion. Adherence of medications is categorized as good (≥ 80% medication taken) or poor (\< 80% medication taken). |
Other
| Measure | Time frame | Description |
|---|---|---|
| The sex-based eradication rate of H. pylori | From enrollment to the end of treatment at 6-8 weeks | The eradication rates are evaluated in females and males, respectively. The investigators define successful eradication as a negative 13C-urea breath test at least four weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by ITT and PP analyses. The ITT analysis evaluates all enrolled participants. The PP analysis evaluates those who take \>= 80% of the study medications and receive post-treatment 13C-urea breath test. The staffs assessing antibiotic sensitivity and the 13C-urea breath test are blinded. |
| The treatment-failure-experience-based eradication rate of H. pylori | From enrollment to the end of treatment at 6-8 weeks | The eradication rates are evaluated in the subjects with naïve, those with once treatment failure experience, those with twice treatment failure experience, those with thrice treatment failure experience, those with four-time treatment failure experience, and those with five-time treatment failure experience, respectively. The investigators define successful eradication as a negative 13C-urea breath test at least four weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by ITT and PP analyses. The ITT analysis evaluates all enrolled participants. The PP analysis evaluates those who take \>= 80% of the study medications and receive post-treatment 13C-urea breath test. The staffs assessing antibiotic sensitivity and the 13C-urea breath test are blinded. |
| The regimen-based eradication rate of H. pylori | From enrollment to the end of treatment at 6-8 weeks | The eradication rates are evaluated in the four regimens, respectively. The investigators define successful eradication as a negative 13C-urea breath test at least four weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by ITT and PP analyses. The ITT analysis evaluates all enrolled participants. The PP analysis evaluates those who take \>= 80% of the study medications and receive post-treatment 13C-urea breath test. The staffs assessing antibiotic sensitivity and the 13C-urea breath test are blinded. |
| The resistance-number-based eradication rate of H. pylori | From enrollment to the end of treatment at 6-8 weeks | The eradication rates are evaluated in the subjects with triple-resistant infection and those with quadruple-resistant infection, respectively. The investigators define successful eradication as a negative 13C-urea breath test at least four weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by ITT and PP analyses. The ITT analysis evaluates all enrolled participants. The PP analysis evaluates those who take \>= 80% of the study medications and receive post-treatment 13C-urea breath test. The staffs assessing antibiotic sensitivity and the 13C-urea breath test are blinded. |
Countries
Taiwan
Outcome results
None listed