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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastritis; Gastric Cancer; Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Pylera; Drug: Esomeprazole 40mg; Drug: Amoxicillin - high dose dual therapy

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Guimarães, Portugal, 4835-044
    • Recruiting
    • Vítor Bruno Macedo da Silva
    • Contact: Vítor Bruno Macedo Silva, M.D.; Phone Number: 00351253540330; Email: vitorbmacedo@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hospital da Senhora da Oliveira

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 28, 2021
• First Posted (ACTUAL): October 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gastritis; Infections; Communicable Diseases; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Esomeprazole
• Other Study ID Numbers: 101/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No