Comparison Between High-dose Amoxicillin Dual Therapy and Pylera Quadruple Therapy in the Treatment of Helicobacter Pylori Infection

Study Overview
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Brief Summary
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Helicobacter pylori is a pathogenic bacteria transmitted from individual to individual, being scientifically recognized as an agent who causes persistent inflammatory activity on the gastric mucosa. This pathogen represents a Global Health problem, as shown in a systematic review by Hooi et al. Besides regional differences, more that half of the world population is expected to have already been infected by this bacteria. In Portugal, research studies estimate that more than 80% of the adult population has already contacted with H. pylori. H. pylori infection is associated with active chronic gastritis in every colonized patient, what may consequently lead to peptic ulcer disease, atrophic gastritis, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. For that reason, H. pylori infection is considered to be a disease, independently of the presence of gastrointestinal symptoms. Additionally, H. pylori has been classified as a confirmed carcinogen (class I) by the International Agency for Research, being responsible for carcinogenic pathways conducting to both gastric adenocarcinoma and lymphoma. This fact gains a particular relevance taking into account that gastric cancer is one of the most prevalent cancers worldwide. On other hand, more than 75% of the gastric cancers occur following H. pylori infection. Thus, H. pylori eradication constitutes an essential Public Health measurement, being inclusively considered a cost-effective method to decrease the gastric cancer burden, by promoting pre-malignant lesions regression, such as atrophic gastritis, and by delaying the disease progression in case of intestinal metaplasia or dysplasia. Maastricht V consensus is a document updated in 2016, including the major recommendations regarding H. pylori diagnosis, follow-up and treatment. It highlights the emergence of antibiotic resistances and how they must influence clinical practice, namely the choice of antibiotic regimens, as successful eradication has become less frequent with more prevalent antibiotic resistances. This is the case of clarithromycin and metronidazol, both currently recommended as first-line options by the Portuguese Society of Gastroenterology. In fact, a systematic review conducted in 2018, aiming to evaluate antibiotic resistances on the Portuguese population observed that clarithromycin, metronidazole and double resistance occurred in 42%, 25% and 20% of the individuals, respectively. Nowadays, Maastricht V guidelines recommend quadruple regimens containing bismuth, such as Pylera (r), as the first-line option in areas with significant double resistance to metronidazole and clarithromycin. Another option currently being investigated is the double therapy with amoxicillin in high doses and proton pump inhibitor. This has become a particularly attractive alternative due to its efficacy, good tolerability and significantly low resistance (<1%) among the European population. The aim of this clinical trial is to compare both regimens - pylera (r) and high-dose amoxycillin - in H. pylori eradication, regarding their efficacy, tolerability and side effects, in order to asses viable therapeutic options in a population with progressively increasing resistances to alternative regimens currently recommended.

Official Title
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Prospective Randomized Trial: Comparison Between High-dose Amoxicillin Dual Therapy and Pylera Quadruple Therapy in the Treatment of Helicobacter Pylori Infection

Conditions
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Helicobacter Pylori Infection, Gastritis, Gastric Cancer

Intervention / Treatment
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* Drug: Amoxicillin - high dose dual therapy
* Drug: Pylera
* Drug: Esomeprazole 40mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented Helicobacter pylori infection Age equal or greater to 18 years Recent (<6months) upper digestive endoscopy Ability to consent to participate in the study Exclusion Criteria: Documented allergy to any of the available drugs Contraindications to any of the available drugs Antibiotics use for the last 4 weeks Previous gastric cancer Previous gastric surgery Pregnancy Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment with Pylera (r) + esomeprazole 40mg<br> | Drug: Pylera<br>* Eradication with Pylera, for 10 days.<br>Drug: Esomeprazole 40mg<br>* Esomeprazole 40mg, twice a day.<br>|
| Active Comparator: Treatment with high-dose amoxicillin + esomeprazole 40mg<br> | Drug: Amoxicillin - high dose dual therapy<br>* Eradication with Amoxicillin 1000mg + 500 mg + 1000mg + 500mg, for 15 days.<br>Drug: Esomeprazole 40mg<br>* Esomeprazole 40mg, twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Helicobacter pylori eradication | Confirmation of H. pylori eradication | Approximately 1 month after treatment |