Susceptibility-Guided Sequential Therapy for Helicobacter Pylori Infection

Study Overview
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Brief Summary
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The main objective of this trial is to assess whether a sequential therapy strategy based on molecular antibiotic susceptibility testing (including clarithromycin and fluoroquinolone) for H. pylori infection will improve the eradication rate compared to an empirical therapy.

Detailed Description
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This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. For empirical therapy group(control group), Bismuth quadruple therapy will be an empirical first-line therapy, and high dose dual (proton-pump inhibitor + amoxicillin) treatment will be for rescue therapy if the first-line empirical treat failure. For the susceptibility-guided sequential therapy group, regimens were selected based on H. pylori susceptibility to clarithromycin and levofloxacin. The primary outcome is the first-line eradication rate in both groups, and the overall (including first- and rescue therapies) H. pylori eradication rates in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis and per-protocol analysis.

Official Title
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Susceptibility-Guided Sequential Therapy Versus Empirical Therapy for Helicobacter Pylori Infection: a Randomised Controlled Trial

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: clarithromycin-sensitive(first-line)
* Drug: clarithromycin-resistant(first-line)
* Drug: empirical therapy group first-line
* Drug: levofloxacin-sensitive(rescue treatment)
* Drug: levofloxacin-resistant(rescue treatment)
* Drug: empirical therapy group rescue treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: H. pylori infection was determined using at least one of the following tests: 13C/14C-urea breath test (UBT), stool H. pylori antigen test, rapid urease test, and histological analysis within 4 weeks. Patients were naïve to H. pylori treatment. Exclusion Criteria: Allergy to any drug administered. Pregnancy and lactation. Major systemic diseases, such as severe cardiopulmonary or liver dysfunction. Complicated with active peptic ulcer disease, gastric cancer, or prior gastrectomy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clarithromycin-sensitive(first-line)<br>If H. pylori is sensitive to clarithromycin, we will administer clarithromycin triple therapy-esomeprazole (20 mg, twice daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily)-for 14 days | Drug: clarithromycin-sensitive(first-line)<br>* esomeprazole (20 mg, twice daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days<br>* Other names: clarithromycin triple therapy;|
| Experimental: clarithromycin-resistant(first-line)<br>If H. pylori is clarithromycin resistance, we selected the High-dose dual therapy (HDDT) regimen as first-line treatment. HDDT-esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily)-will be used for 14 days. | Drug: clarithromycin-resistant(first-line)<br>* esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily) for 14 days<br>* Other names: High-dose PPI-amoxicillin dual therapy;|
| Active Comparator: empirical therapy group first-line<br>The empirical therapy group will receive Bismuth-containing quadruple therapy(BQT) as first-line treatment, The BQT regime is comprising of esomeprazole (20 mg, twice daily), colloidal bismuth pectin (150 mg, four times daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days. | Drug: empirical therapy group first-line<br>* esomeprazole (20 mg, twice daily), colloidal bismuth pectin (150 mg, four times daily), clarithromycin (500 mg, twice daily), and amoxicillin (1.0 g, twice daily) for 14 days<br>* Other names: Bismuth-containing quadruple therapy;|
| Experimental: levofloxacin-sensitive(rescue treatment)<br>If H. pylori was levofloxacin-sensitive, we will use the levofloxacin quadruple regimen as rescue treatment-esomeprazole (20 mg, twice daily), levofloxacin (500 mg, once daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily)-for 14 days. | Drug: levofloxacin-sensitive(rescue treatment)<br>* esomeprazole (20 mg, twice daily), levofloxacin (500 mg, once daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily) for 14 days<br>* Other names: levofloxacin quadruple regimen;|
| Experimental: levofloxacin-resistant(rescue treatment)<br>If H. pylori was levofloxacin-resistant, we will use furazolidone quadruple regimen as rescue treatment-esomeprazole (20 mg, twice daily), furazolidone (100 mg, twice daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily)-for 14 days. | Drug: levofloxacin-resistant(rescue treatment)<br>* esomeprazole (20 mg, twice daily), furazolidone (100 mg, twice daily), amoxicillin (1.0 g, twice daily), and colloidal bismuth pectin (150 mg, four times daily) for 14 days<br>* Other names: furazolidone quadruple regimen;|
| Active Comparator: empirical therapy group rescue treatment<br>If BQT fails, HDDT-esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily)-will be used as a rescue treatment for 14 days. | Drug: empirical therapy group rescue treatment<br>* esomeprazole (20 mg, four times daily) and amoxicillin (750 mg, four times daily) for 14 days<br>* Other names: High-dose PPI-amoxicillin dual therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the first-line H. pylori eradication rate | the proportion of participants with successful H. pylori eradication, as determined by 13C-Urea breath test(UBT), at least 4 weeks after the end of the first-line treatment period between Susceptibility-guided therapy(SGT) and empirical therapy(ET) group. | 4-8 weeks after the end of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rescue H. pylori eradication rate | The second line eradication rate between SGT and ET group. | 4-8 weeks after the second treatment | 
| the overall H.pylori eradication rate | the total H.pylori eradication rate (first-line and second-line)between SGT and ET group. | 4-8 weeks after the second treatment | 
| high-dose dual therapy eradication rate | compare H. pylori eradication rate between clarithromycin resistance group and empirical BQT failure group. | 4-8 weeks after the second treatment | 
| Adverse events and compliance | 3 days after the completion of therapy according to a data collection form | 3 days after the end of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori, Drug Resistance, Microbial, Microbial Sensitivity Tests