Sequential Therapy Versus Quadruple Therapy as Second Line Treatment After Failure of the Standard Triple Therapy for H Pylori Infection

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy of sequential therapy, i.e. 5 days of PPI + amoxicillin followed by 5 days of PPI + two antimicrobial drugs( clarithromycin and tinidazole ) versus quadruple drug regimen( i.e.-14 days of PPI+ bismuth + metronidazole + tetracycline ) as second line treatment of H. pylori .

Detailed Description
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a total of 101 patients were randomized to 2 groups : 50 in sequential group and 51 patients in quadruple group . mean age was 43 in both groups. In sequential therapy group 42 patients(84%) completed the treatment , 39 patients returned to follow up . In quadruple group only 33 patients (64.7%) completed the treatment , 29 of them returned to follow up. Compliance to the treatment was significant better in sequential group comparative to quadruple .Sides effects connected to gastro-intestinal tract were reported in 27(65.9%) of quadruple group patients and in 19(43.2%)of sequential group. The H pylori was eradicated in 23 of 39 patients in sequential group(59%), and in 19 of the 29 patients in quadruple group(65.5%). no comorbidities like smoking, diabetes or other influenced the efficacy of eradication. Sequential therapy showed the same eradication rate as second line treatment of H pylori as quadruple one, but was associated with better compliance and less adverse effects. Both treatments protocols failed to show an appropriate eradication rate in population of Southern Israel .

Conditions
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Optimization of Second Line Treatment Protocol for H Pylori Eradication

Intervention / Treatment
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* Drug: Lansoprazole , Tab Amoxycillin , Tab Clarithromycin ,Tab Tinidazole
* Drug: Lansoprazole, Bismuth Subsalicylate, Metronidazole, Tetracycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent age at least 18 years persisting H.pylori infection after at least one course of first-line standard triple therapy (Amoxycillin, Clarithromycin or Metronidazole based) Exclusion Criteria: history of gastrectomy gastric malignancy, including adenocarcinoma and lymphoma previous allergic reaction to antibiotics (amoxicillin, clarithromycin, metronidazole, tetracycline) and proton pump inhibitors Active upper gastrointestinal bleeding within the previous 1 week contraindications to the treatment drugs Pregnant or lactating women Severe concurrent disease or malignancy

Ages Eligible for Study
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Minimum Age: 18 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: sequential treatment<br>1.drugs experimental-Sequential -PPI( Lansoprazole 30mg x2/day) + amoxicillin 1gx2/day for 5days, followed by 5 days of PPI(Lansoprazole 30mg x2/day) + ( Clarithromycin500mg x2/day and Tinidazole 500mg x2/day ) | Drug: Lansoprazole , Tab Amoxycillin , Tab Clarithromycin ,Tab Tinidazole<br>* use of Sequential therapy as second line treatment for eradication H pylori currently Sequential therapy is indicated as first line treatment for H pylori eradication<br>|
| Active Comparator: quadruple therapy<br>Quadruple drug regimen (i.e.-14 days of PPI (Lansoprazole 30mg x2/day) + Bismuth Subsalicylate 525mg X4/day + Metronidazole 500mg x3/day + Tetracycline 500mg x4/day )-is standard of care as second line treatment in eradication of H pylori | Drug: Lansoprazole, Bismuth Subsalicylate, Metronidazole, Tetracycline<br>* this combination is standard of care as H pylori second line treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The eradication rate after second line treatment based on sequential therapy comparative to eradication rate after second line therapy based on quadriple regimen | H pylori eradication is defined as a negative C-urea breath test 4-16 weeks after completion of tratment.]. (C-urea breath test- Patients are fasted for 4 h before testing. No test meal will be given, and a pre-dose breath sample is obtained. 75 mg of 13C-urea powder dissolved in 50 mL of water is then administered orally, and a second breath sample is collected 30 minutes later. Collected samples are analyzed using an isotope ratio mass spectrometer). | 18 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary end points: Adverse effects of sequential and quadruple treatment | -Adverse effects -taste alteration , peripheral neuropathy, seizures, nausea, vomiting, diarrhea, abdominal pain, allergic reaction, photo sensibility-checked at clinical visit by direct question. | 18 months | 
| compliance with treatment | compliance is considered to be satisfactory when drug intake exceeded 80 %( by pills count). | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H pylori, sequential therapy, second line treatment