Helicobacter Pylori Eradication Therapy in Portugal

NCT05449028 | Unknown

• 1 other identifier: HpETIP
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Helicobacter pylori (H. pylori) infection remains a major public health problem, with an estimated prevalence of over 50% worldwide and 60-86% for Portugal. H. pylori is associated with significant morbidity and mortality from peptic ulcerative disease to gastric cancer, whose eradication therapy has proven to be effective in preventing these complications. Factors involved in the development of these conditions include H. pylori virulence, host genetic factors and gut microbiota. Given the increasing pattern of antibiotic resistance evidenced by this bacterium and the scarcity of available antibiotic therapy, both in Portugal and worldwide, there is not enough evidence on the best eradication strategy. Regarding the uncertainties about the potential negative impact of indiscriminate use of eradication therapy on gut microbiota, either by proton pump inhibitors or by antibiotics per se, there is an overriding need for evidence about the real impact of this therapy on oral or gut flora and possible clinical consequences in immunological, metabolic, nutritional and oncological terms. Objectives: Comparative evaluation of the efficacy of the different quadruple therapy regimens recommended for the H. pylori eradication. Comparative evaluation of the safety profile in terms of clinical, and immunological and gut microbiota impact of the different therapies for the H. pylori eradication.

Conditions

Helicobacter Pylori; Gut Microbiota; Immunology

Outcome Measures

Primary Outcomes (4)

• Efficacy assessed by the eradication rate of the different therapeutic regimens recommended as H. pylori eradication therapy

  Efficacy rate of H. pylori eradication will be determined for five different therapeutic regimens (sequential, hybrid and concomitants with or without bismuth). A successful eradication implies no documentation of H. pylori by carbon 13-labeled urea breath test or upper gastrointestinal endoscopy with biopsies, depending on clinical indication, at 1 month after H. pylori eradication (D40 or D44). A therapeutic regimen will be considered effective if it achieves more than 90% of H. pylori eradication (the minimum efficacy rate).

  1 month after the intervention

• Efficacy assessed by the re-infection rate after the different therapeutic regimens recommended as H. pylori eradication therapy

  At 12 months after H. pylori eradication, a carbon 13-labeled urea breath test will be performed to exclude re-infection.

  12 months after the intervention

• Safety assessed by overall treatment-adverse events and and severe treatment-adverse events rates of the different therapeutic regimens recommended as H. pylori eradication therapy

  Safety profile of H. pylori eradication will be determined for five different therapeutic regimens measuring adverse effects according to Medical Dictionary for Regulatory Activities (MedDRa). Therapy-related adverse events and its severity (by visual analogue scale of intolerance \[0-10\] and classification of the severity of adverse effects for the daily life activities according to \[BoThBo96\]) will be recorded at 1 month post-eradication follow-up.

  1 month after the intervention

• Safety assessed by overall treatment completion rate of the different therapeutic regimens recommended as H. pylori eradication therapy

  Safety profile of H. pylori eradication will be determined for five different therapeutic regimens measuring the treatment completion rate to the treatment at 1 month post-eradication follow-up.

  1 month after the intervention

Secondary Outcomes (2)

• Post-eradication changes assessed by OTU and their relative abundance in gut microbiota

  Changes from baseline at immediately after the intervention

• Post-eradication changes assessed by OTU and their relative abundance in gut microbiota

  Changes from baseline at 1 month after the intervention

Other Outcomes (2)

• Post-eradication changes assessed by immunological cells populations in immunological profile

  Changes from baseline at 12 months after the intervention

• Post-eradication changes assessed by cytokines, chemokines and growth factors in immunological profile

  Changes from baseline at 12 months after the intervention

Study Arms (5)

H. pylori eradication scheme A

EXPERIMENTAL

Esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 8/8h, for 14 days

Drug: H. pylori eradication scheme A

H. pylori eradication scheme B

EXPERIMENTAL

Esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h, for 14 days

Drug: H. pylori eradication scheme B

H. pylori eradication scheme C

EXPERIMENTAL

Esomeprazole 40mg bid + bismuth subsalicylate 420mg 6/6h + metronidazole 375mg 6/6h + tetracycline 375mg 6/6h, for 10 days

Drug: H. pylori eradication scheme C

H. pylori eradication scheme D

EXPERIMENTAL

Esomeprazole 40mg bid + amoxicillin 1g 12/12h for 7 days, followed by esomeprazole 40mg bid + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h for 7 days

Drug: H. pylori eradication scheme D

H. pylori eradication scheme E

EXPERIMENTAL

Esomeprazole 40mg bid + amoxicillin 1g 12/12h for 7 days, followed by esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h for 7 days

Drug: H. pylori eradication scheme E

Interventions

H. pylori eradication scheme A DRUG

Esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 8/8h, for 14 days

Also known as: Concomitant bismuth-free A

H. pylori eradication scheme A

H. pylori eradication scheme B DRUG

Esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h, for 14 days

Also known as: Concomitant bismuth-free B

H. pylori eradication scheme B

H. pylori eradication scheme C DRUG

Esomeprazole 40mg bid + bismuth subsalicylate 420mg 6/6h + metronidazole 375mg 6/6h + tetracycline 375mg 6/6h, for 10 days

Also known as: Pylera, Concomitant with bismuth

H. pylori eradication scheme C

H. pylori eradication scheme D DRUG

Esomeprazole 40mg bid + amoxicillin 1g 12/12h for 7 days, followed by esomeprazole 40mg bid + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h for 7 days

Also known as: Sequential

H. pylori eradication scheme D

H. pylori eradication scheme E DRUG

Esomeprazole 40mg bid + amoxicillin 1g 12/12h for 7 days, followed by esomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h for 7 days

Also known as: Hybrid

H. pylori eradication scheme E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gastric infection by H. pylori by histological examination of gastric biopsies or carbon 13-labeled urea breath test.

You may not qualify if:

• Age \< 18 years;
• Pregnant, breast-feeding or women of childbearing age who do not comply with effective anticonception measures;
• History of allergy, hypersensitivity or contraindication to the use of H. pylori eradication drugs (antibiotics or proton pump inhibitors);
• History of previous gastrointestinal surgery or neoplasia;
• Previous H. pylori eradication therapies; Antibiotic or probiotic therapies in the month prior to recruitment;
• Use of proton pump inhibitors, other antacids or gastric mucosal protection agents in the 2 weeks prior to recruitment;
• Corticosteroids or immunomodulatory therapy in the month prior to recruitment;
• Immunodeficiency;
• Insulin-treated diabetes mellitus;
• Obesity (Body mass index ≥30Kg/m2);
• Use of laxative therapy in the 15 days prior to recruitment;
• Decompensated heart, liver, kidney or respiratory diseases and;
• Refusal or inability to give informed consent.

Sponsors & Collaborators

• Unidade Local de Saúde de Coimbra, EPE: lead
• University of Coimbra: collaborator

Study Sites (1)

Centro Hospitalar e Universitário de Coimbra

Coimbra, 3000-075, Portugal

RECRUITING

Related Publications (28)

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MeSH Terms

Interventions

Bismuth

Intervention Hierarchy (Ancestors)

Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Radioisotopes; Isotopes; Metals

Study Officials

• Elisa Gravito-Soares, MD

  Unidade Local de Saúde de Coimbra, EPE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisa Gravito-Soares, MD

CONTACT

(+351)239400483; es18497@gmail.com

Nuno Almeida, PhD

CONTACT

(+351)239400483; nunoperesalmeida@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sampling: Consecutive sampling of incident cases of patients with H. pylori gastric infection and clinical indication for its eradication; Patients will be continuously monitored throughout the study. Regarding the evaluation of oral and gut microbiota and immunological changes, the study will be blinded, since the researchers responsible for sequencing and immunological analysis will not know the therapeutic scheme applied.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: An interventional study is proposed to compare the efficacy and safety of the different approved H. pylori eradication quadruple regimens. Patients will be randomly assigned to the five quadruple regimens arms (A, B, C D and E). All patients will be followed during 12 months. A standardized protocol will be applied for all the groups, differing only in type of quadruple regimen used.

Study Record Dates

• First Submitted: May 22, 2022
• First Posted: July 8, 2022
• Study Start: May 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: July 8, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)