Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice

Study Overview
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Brief Summary
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Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer and gastric tumors (adenocarcinoma and lymphoma). The cure of the H. pylori infection prevents recurrence of duodenal and gastric ulcer and improves dyspepsia in a significant proportion of cases, so it is cost-effective. Eradication therapy has changed over time. The usually recommended pattern in the consensus conferences has traditionally been triple therapy, composed by the combination of 2 antibiotics (clarithromycin plus amoxicillin or metronidazole) and a proton pump inhibitor (PPI) for 7-14 days. Recent meta-analyses have that the current global eradication rate after standard triple therapy is less than 80%. Several European studies have found even lower eradication rates, with 35-40% of cases resulting in treatment failure. Treatment failure leads to a second treatment and a new diagnostic test to confirm eradication.

Detailed Description
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Justification of the study: One of the latest therapeutic innovations is sequential therapy, introduced in Italy by Zullo et al. The drug delivery strategy involves a 5-day induction phase with dual therapy (a PPI every 12 hours and amoxicillin 1g every 12 hours), followed immediately by triple therapy for 5 days with a PPI every 12 hours, metronidazole 500 mg every 12 hours and clarithromycin 500 mg every 12 hours. Sequential therapy has proved more effectiveness than standard triple therapy for seven and ten days. In order to assess the efficacy of this new treatment in our area, over the past year we conducted a multicentre observational pilot study in routine clinical practice conditions in patients infected with H. pylori and with indications for eradication. 139 patients from 6 different centres were included. Excellent treatment compliance and minimal side effects, similar to those described with triple therapy, were shown. The results confirm similar efficacy to that obtained in previous studies and an eradication rate significantly higher than that obtained with classic triple therapy in our area. Several previous studies have shown excellent efficacy of quadruple therapy with a PPI, amoxicillin, clarithromycin and metronidazole, administering concomitantly the same drugs as those of sequential therapy, but only for 5-7 days. Several studies have found a higher eradication rate of this concomitant therapy as compared with classic triple therapy. The results of a randomized study in which sequential and concomitant therapy were compared have recently been reported in the American Congress of Gastroenterology. Eradication and adverse events rates were similar with both treatments. This data suggest that the sequentiallyadministration of these drugs probably complicated unnecessarily the treatment. Therefore it is necessary to make a controlled clinical trial to directly compare sequential versus concomitant therapy. The results of this study will conclude which should be the first line treatment for H. pylori eradication.

Official Title
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Phase 4, Prospective, Randomized and Comparative Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice

Conditions
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Helicobacter Pylori

Intervention / Treatment
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* Drug: PPI, amoxicillin, metronidazole and clarithromycin
* Drug: PPI, amoxicillin, metronidazole and clarithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion of patients with dyspepsia or peptic gastroduodenal ulcer for whom eradication treatment is indicated. Requirement of confirmation of the diagnosis of H. pylori infection by at least one positive test out of the following: breath test, histology, rapid urease test or culture. Exclusion Criteria: Age less than 18 years. Advanced chronic disease or any other pathology that prevents attending controls and follow up. Allergy to any of the antibiotics in the treatment. Previous gastric surgery Pregnancy and lactation. History of alcohol or drug abuse. Previous eradication treatment. Consumption of antibiotics or bismuth salts during the last 4 weeks

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 |
| --- | --- |
| Active Comparator: Sequential treatment:<br> | Drug: PPI, amoxicillin, metronidazole and clarithromycin<br>* Dual therapy for 5 days: PPI and 1g amoxicillin every 12h. After dual therapy continue with a triple therapy for 5 days: PPI, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.<br>|
| Experimental: Concomitant treatment<br> | Drug: PPI, amoxicillin, metronidazole and clarithromycin<br>* Quadruple therapy for ten days:PPI, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intention to treat eradication rates | Intention-to-treat eradication of infection. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per protocol Eradication rate | Per protocol eradication of infection. | One year | 
| Compliance | Treatment compliance | One year | 
| Adverse events | Adverse events | One year | 
| Clinical and demographic variables | Age Sex Smoking habits Comorbidity (diabetes mellitus, arterial hypertension, ischemic heart disease, dyslipidemia, others) Indication for eradication (peptic ulcer vs. uninvestigated or functional dyspepsia) Initial diagnostic test for H. pylori infection. | One year |