Comparison of Two Novel First-line Anti-Helicobacter Pylori Therapy

Study Overview
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Brief Summary
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The Asian-Pacific Consensus Report has recommended that proton pump inhibitor (PPI)-clarithromycin-amoxicillin or metronidazole treatment for 7 to14 days is the first choice treatment for H pylori infection. As a general rule for the treatment of other infectious diseases, clinicians should prescribe therapeutic regimens that have a per-protocol eradication rate ≥ 90% for anti-H pylori therapy. However, the eradication rate of the standard triple therapy has generally declined to unacceptable levels (i.e., 80% or less) recently. The reasons for this fall in efficacy with time may relate to the increasing incidence of clarithromycin-resistant strains of H. pylori. Clarithromycin resistance is the major cause of eradication failure for stand triple therapy. Standard triple therapies should be abandoned in the areas with clarithromycin resistance ≥ 20% because the per-protocol eradication rates of standard therapies are often less than 85% and the intention-to-treat eradication rates are usually less than 80%..7-10 day non-bismuth containing quadruple therapy (Concomitant therapy) had been successful in the presence of clarithromycin resistance. Another novel treatment with 14-day high dose PPI and amoxicilin dual therapy could also attained >90 eradication rate in some studies. This novel treatment is simple and involved only two drugs and the most important of all is that amoxicillin resistance is still 0% in Taiwan . High dose PPI has been used in several studies for H. pylori eradication in order to increase the intra-gastric PH for optimal eradication So far, there is still unclear which one is the best first-line H. pylori eradication regimen with highest eradication rate and least adverse effects. We therefore design a randomized controlled trial to simultaneously assess the efficacy novel 14-day high dose dual therapy by comparing to the 7-day non-bismuth containing quadruple therapy in Taiwan and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies.

Detailed Description
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The Asian-Pacific Consensus Report has recommended that proton pump inhibitor (PPI)-clarithromycin-amoxicillin or metronidazole treatment for 7 to14 days is the first choice treatment for H pylori infection. As a general rule for the treatment of other infectious diseases, clinicians should prescribe therapeutic regimens that have a per-protocol eradication rate ≥ 90% for anti-H pylori therapy. However, the eradication rate of the standard triple therapy has generally declined to unacceptable levels (i.e., 80% or less) recently.[3-9] The reasons for this fall in efficacy with time may relate to the increasing incidence of clarithromycin-resistant strains of H. pylori. The main reasons for eradication failure for H pylori infection include antibiotic resistance, poor compliance and rapid metabolism of PPI. Clarithromycin resistance is the major cause of eradication failure for stand triple therapy. The rate of clarithromycin-resistant strains ranged from 49% (Spain) to 1% (Netherland) worldwide. Standard triple therapies should be abandoned in the areas with clarithromycin resistance ≥ 20% because the per-protocol eradication rates of standard therapies are often less than 85% and the intention-to-treat eradication rates are usually less than 80%. 7-10 day non-bismuth containing quadruple therapy (Concomitant therapy) had been successful in the presence of clarithromycin resistance. Another novel treatment with 14-day high dose PPI and amoxicilin dual therapy could also attained >90 eradication rate in some studies. This novel treatment is simple and involved only two drugs and the most important of all is that amoxicillin resistance is still 0% in Taiwan. High dose PPI has been used in several studies for H. pylori eradication in order to increase the intra-gastric PH for optimal eradication So far, there is still unclear which one is the best first-line H. pylori eradication regimen with highest eradication rate and least adverse effects. We therefore design a randomized controlled trial to simultaneously assess the efficacy novel 14-day high dose dual therapy by comparing to the 7-day non-bismuth containing quadruple therapy in Taiwan and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies.

Official Title
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Comparison of Two Novel First-line Anti-Helicobacter Pylori Therapy: A Prospective Randomized Trial

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: Nexium
* Drug: Amolin
* Drug: Klaricid
* Drug: Flagyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. H. pylori-infected outpatients with endoscopically proven peptic ulcer diseases or gastritis. Exclusion Criteria: Previous H. pylori-eradication therapy ingestion of antibiotics, bismuth, or PPIs within the prior 4 weeks patients with allergic history to the medications used patients with previous gastric surgery the coexistence of serious concomitant illness (for example, decompensated liver cirrhosis, uremia) pregnant women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose dual therapy<br>Esomeprezole (Nexium)40 mg tid. and amoxicillin (Amolin) 750 mg qid. for 14 days | Drug: Nexium<br>* Esomeprazole ( Nexium )40 mg tid daily for 14 days in the high dose dual therapyarm and 40 mg bid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Esomeprazole;Drug: Amolin<br>* Amoxicillin 750 mg qid daily for 14 days in the high dose dual therapy and amoxicillin 1 g bid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Amoxicillin;|
| Active Comparator: Non-bismuth quadruple therapy<br>Esomeprezole (Nexium) 40 mg bid.,clarithromycin (Klaricid) 500 mg bid., amoxicillin (Amolin) 1 g bid. and metronidazole (Flagyl) 500 mg bid. for 7 days | Drug: Nexium<br>* Esomeprazole ( Nexium )40 mg tid daily for 14 days in the high dose dual therapyarm and 40 mg bid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Esomeprazole;Drug: Amolin<br>* Amoxicillin 750 mg qid daily for 14 days in the high dose dual therapy and amoxicillin 1 g bid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Amoxicillin;Drug: Klaricid<br>* clarithromycin 500 mg bid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Clarithromycin;Drug: Flagyl<br>* Metronidazole (Flagyl) 500 mg tid daily for 7 days in the non-bismuth quadruple therapy<br>* Other names: Metronidazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rates of H.pylori eradication | The primary outcome variables were the rates of eradication. Chi-square test with or without Yates correction for continuity and Fisher's exact test were used when appropriate to compare the major outcomes between groups. A P value less than 0.05 was considered statistically significant. | 6-8 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori eradication, High dose proton pump inhibitor, High dose Amoxicillin, Concomitant therapy