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Helicobacter PyloriNCT05449028

Helicobacter Pylori Eradication Therapy in Portugal

A study testing H. pylori eradication scheme A, H. pylori eradication scheme B and H. pylori eradication scheme C in people with Helicobacter Pylori and Gut Microbiota, run by Unidade Local de Saúde de Coimbra, EPE at 1 site in Portugal.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Helicobacter Pylori, Gut Microbiota, Immunology
What is being tested?
H. pylori eradication scheme A, H. pylori eradication scheme B and H. pylori eradication scheme C
Could I receive a placebo?
No, everyone receives an active treatment
How many people
230 participants
Where
1 sitePortugal
Study dates
1 May 2022to 31 Dec 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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;
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Elisa Gravito-Soares, MD contact

(+351)239400483

es18497@gmail.com

Nuno Almeida, PhD contact

(+351)239400483

nunoperesalmeida@gmail.com

Portugal1 site, 1 recruiting

  • Centro Hospitalar e Universitário de Coimbra

    Coimbra, 3000-075

    Elisa Gravito-Soares, MD, (+351)239400483, es18497@gmail.com

    Nuno Almeida, PhD, (+351)239400483, nunoperesalmeida@gmail.com

    Recruiting

Other trials in Portugal

About this study

Official title: Helicobacter Pylori Eradication Therapy in Portugal: Prospective, Randomized, Blind and Multicentre Trial on the Efficacy of Quadruple Therapies and Their Clinical Impact, and Immunological and Gut Microbiota Changes

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.

Read the detailed description

Introduction: 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.

Methods: Prospective longitudinal multicentre study of total of patients with gastric infection by H. pylori, diagnosed by 13C-urea breath test or histological analysis of gastric biopsies and clinical indication for its eradication, referred to the different participating Portuguese hospital units and a blind randomized controlled clinical trial of the efficacy and safety of the different quadruple therapy regimes recommended for the H. pylori eradication. This study will be carried out in 4 phases: Phase 1 - Recruitment and randomization of patients by the different quadruple eradication schemes with and without bismuth (5 parallel arms); Phase 2 - H. pylori eradication with evaluation of the efficacy and safety rates at 1 month and the absence of reinfection at 12 months after treatment and collection of stool samples before and after the eradication therapy for evaluation of changes in gut microbiota; Phase 3 - Analysis of richness, diversity and uniformity of gut microbiota by DNA sequencing using the hypervariable region of the ribosomal 16S bacteria gene as a taxonomic identification marker and their clinical impact on immunology, metabolism and nutrition at 12 months after the H. pylori eradication therapy; and Phase 4 - Analysis of immunological changes through the study of cell populations by flow cytometry (CD4+, CD8+, B-cell, T-cell, natural killer cells, cells ratio) and cytokines, chemokines and growth factors by xMAP/Luminex before and 12 months after the H. pylori eradication therapy.

Expected results, impact and scientific outputs: Given the high rate of triple therapy inefficacy, high antibiotic resistance and the scarcity and controversy of existing literature on quadruple regimens, there may be relevant differences in the approved quadruple regimens for the H. pylori eradication, being necessary to define which is the most effective and safe in Portugal, decreasing the rate of ineffectiveness and exposure to multiple antibiotics. The homeostasis of gut microbiota is significantly changed after H. pylori eradication and this modification may be substantially different according to the therapeutic scheme used, with clinical implications on immunology, metabolism and nutrition. Thus, a randomized trial to compare quadruple regimens is need, allowing in the future, an individualized selection of the H. pylori eradication regimen, taking into account the higher efficacy and safety and lower gut dysbiosis and its systemic consequences, in short and long term. Modulating oral and gut microbiota therapies, including prebiotics, probiotics, symbiotics, fecal microbiota transplantation and perhaps targeted-immunotherapy may be beneficial as adjuvant therapy to existing H. pylori eradication regimens, in a systematic way or for some therapeutic regimes or risk groups.

Being tested
H. pylori eradication scheme A, H. pylori eradication scheme B, H. pylori eradication scheme C, H. pylori eradication scheme D, H. pylori eradication scheme E

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • H. pylori eradication scheme ADrug

    Also called Concomitant bismuth-free A

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

  • H. pylori eradication scheme BDrug

    Also called Concomitant bismuth-free B

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

  • H. pylori eradication scheme CDrug

    Also called Pylera, Concomitant with bismuth

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

  • H. pylori eradication scheme DDrug

    Also called Sequential

    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

  • H. pylori eradication scheme EDrug

    Also called Hybrid

    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

Study groups in NCT05449028
Study groupRoleWhat they receive
H. pylori eradication scheme AExperimentalEsomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 8/8h, for 14 days
Receives: Drug: H. pylori eradication scheme A
H. pylori eradication scheme BExperimentalEsomeprazole 40mg bid + amoxicillin 1g 12/12h + clarithromycin 500mg 12/12h + metronidazole 500mg 12/12h, for 14 days
Receives: Drug: H. pylori eradication scheme B
H. pylori eradication scheme CExperimentalEsomeprazole 40mg bid + bismuth subsalicylate 420mg 6/6h + metronidazole 375mg 6/6h + tetracycline 375mg 6/6h, for 10 days
Receives: Drug: H. pylori eradication scheme C
H. pylori eradication scheme DExperimentalEsomeprazole 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
Receives: Drug: H. pylori eradication scheme D
H. pylori eradication scheme EExperimentalEsomeprazole 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
Receives: Drug: H. pylori eradication scheme E

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 1 month after the intervention

  2. 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.

    Measured: 12 months after the intervention

  3. 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.

    Measured: 1 month after the intervention

  4. 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.

    Measured: 1 month after the intervention

Secondary outcomes (2)

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

    Stool samples shall be collected, stored at -20°C and then analyzed on 3 occasions: 1) baseline, 2) after stopping treatment (D10 or 14) and 3) 1 month after treatment (D40 or 44). A standard protocol with the conditions of collection, storage and transport of the different collected samples will be used. Analysis of gut microbiota by DNA sequencing using the hypervariable region of the 16S ribosomal bacteria gene as a taxonomic identification marker by bioinformatic analysis, for taxonomic identification and determination of the relative abundance of each Operational Taxonomy Units (OTU). The gut microbiota will be evaluated by an independent operator who does not know the therapeutic scheme used.

    Measured: Changes from baseline at immediately after the intervention

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

    Stool samples shall be collected, stored at -20°C and then analyzed on 3 occasions: 1) baseline, 2) after stopping treatment (D10 or 14) and 3) 1 month after treatment (D40 or 44). A standard protocol with the conditions of collection, storage and transport of the different collected samples will be used. Analysis of gut microbiota by DNA sequencing using the hypervariable region of the 16S ribosomal bacteria gene as a taxonomic identification marker by bioinformatic analysis, for taxonomic identification and determination of the relative abundance of each Operational Taxonomy Units (OTU). The gut microbiota will be evaluated by an independent operator who does not know the therapeutic scheme used.

    Measured: Changes from baseline at 1 month after the intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2022
  2. Study start1 May 2022
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
230 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05449028
Sponsor's protocol ID
HpETIP
Status last verified
Jul 2022
First submitted
22 May 2022
Last updated
8 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No applicable.

Publications

  • Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017 Aug;153(2):420-429. doi: 10.1053/j.gastro.2017.04.022. Epub 2017 Apr 27.

    PubMed 28456631

  • Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh-Navaei R, Shokri-Shirvani J, Derakhshan MH. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018 Apr;47(7):868-876. doi: 10.1111/apt.14561. Epub 2018 Feb 12.

    PubMed 29430669

  • Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.

    PubMed 27707777

  • Gao JJ, Zhang Y, Gerhard M, Mejias-Luque R, Zhang L, Vieth M, Ma JL, Bajbouj M, Suchanek S, Liu WD, Ulm K, Quante M, Li ZX, Zhou T, Schmid R, Classen M, Li WQ, You WC, Pan KF. Association Between Gut Microbiota and Helicobacter pylori-Related Gastric Lesions in a High-Risk Population of Gastric Cancer. Front Cell Infect Microbiol. 2018 Jun 19;8:202. doi: 10.3389/fcimb.2018.00202. eCollection 2018.

    PubMed 29971220

  • Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-239. doi: 10.1038/ajg.2016.563. Epub 2017 Jan 10.

    PubMed 28071659

  • Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology. 2018 Nov;155(5):1372-1382.e17. doi: 10.1053/j.gastro.2018.07.007. Epub 2018 Jul 7.

    PubMed 29990487

  • Lopo I, Libanio D, Pita I, Dinis-Ribeiro M, Pimentel-Nunes P. Helicobacter pylori antibiotic resistance in Portugal: Systematic review and meta-analysis. Helicobacter. 2018 Aug;23(4):e12493. doi: 10.1111/hel.12493. Epub 2018 Jun 17.

    PubMed 29911329

  • Almeida N, Romaozinho JM, Donato MM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Fernandes A, Calhau C, Sofia C. Helicobacter pylori antimicrobial resistance rates in the central region of Portugal. Clin Microbiol Infect. 2014 Nov;20(11):1127-33. doi: 10.1111/1469-0691.12701. Epub 2014 Jul 12.

    PubMed 24890952

  • Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177-86.e3; Discussion e12-3. doi: 10.1016/j.cgh.2013.05.028. Epub 2013 Jun 8.

    PubMed 23751282

  • Cerqueira RM, Manso MC, Correia MR, Fernandes CD, Vilar H, Nora M, Martins P. Helicobacter pylori eradication therapy in obese patients undergoing gastric bypass surgery--fourteen days superior to seven days? Obes Surg. 2011 Sep;21(9):1377-81. doi: 10.1007/s11695-010-0254-4.

    PubMed 20838918

  • Almeida N, Donato MM, Romaozinho JM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Fernandes A, Calhau C, Sofia C. Beyond Maastricht IV: are standard empiric triple therapies for Helicobacter pylori still useful in a South-European country? BMC Gastroenterol. 2015 Feb 15;15:23. doi: 10.1186/s12876-015-0245-y.

    PubMed 25886722

  • Boal Carvalho P, Magalhaes J, Dias de Castro F, Rosa B, Cotter J. Randomized Controlled Trial for Helicobacter pylori Eradication in a Naive Portuguese Population: Is Sequential Treatment Superior to Triple Therapy in Real World Clinical Setting? Acta Med Port. 2017 Mar 31;30(3):185-189. doi: 10.20344/amp.8072. Epub 2017 Mar 31.

    PubMed 28550827

  • Cerqueira RM, Correia M, Vilar H, Manso MC. Cumulative Helicobacter Pylori Eradication Rates by Adopting First- and Second- Line Regimens Proposed by the Maastricht IV Consensus in Obese Patients Undergoing Gastric Bypass Surgery. Obes Surg. 2018 Mar;28(3):743-747. doi: 10.1007/s11695-017-2915-z.

    PubMed 29076008

  • Heimesaat MM, Fischer A, Plickert R, Wiedemann T, Loddenkemper C, Gobel UB, Bereswill S, Rieder G. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils. PLoS One. 2014 Jun 18;9(6):e100362. doi: 10.1371/journal.pone.0100362. eCollection 2014.

    PubMed 24941045

  • Myllyluoma E, Ahlroos T, Veijola L, Rautelin H, Tynkkynen S, Korpela R. Effects of anti-Helicobacter pylori treatment and probiotic supplementation on intestinal microbiota. Int J Antimicrob Agents. 2007 Jan;29(1):66-72. doi: 10.1016/j.ijantimicag.2006.08.034. Epub 2006 Dec 1.

    PubMed 17141481

Questions about this trial

What is this clinical trial studying?

A study testing H. pylori eradication scheme A, H. pylori eradication scheme B and H. pylori eradication scheme C in people with Helicobacter Pylori and Gut Microbiota, run by Unidade Local de Saúde de Coimbra, EPE at 1 site in Portugal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Elisa Gravito-Soares, MD ((+351)239400483, es18497@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy assessed by the eradication rate of the different therapeutic regimens recommended as H. pylori eradication therapy (time frame: 1 month after the intervention). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05449028, which also lists 28 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2022.

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