A "Screen and Treat" Helicobacter Pylori Eradication Trial in Adolescents in Three Regions of Chile

NCT05926804 | Recruiting

• 1 other identifier: 1220964
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 3

Brief Summary

Gastric cancer remains a global health problem, and Chile has one of the highest GC mortality rates in the region. Helicobacter pylori (H. pylori) infection is ubiquitous in Chilean adults, and it constitutes the main cause of GC worldwide. A long-term process occurs from premalignant lesions to carcinoma. H. pylori eradication during early stages of disease significantly impacts outcomes, favoring survival, disease reversal and molecular changes, which supports a "screen and treat" strategy in asymptomatic populations in areas with intermediate-to-high GC prevalence. The Investigators' previous research has shown that H. pylori infection is acquired in early childhood with low rates of spontaneous eradication. A pilot treatment study in a subset of school-aged asymptomatic children showed a high rate of successful eradication (\>95%), good tolerance, and was associated with a decrease in serum biomarkers of gastric damage (pepsinogen I and II). Based on the results of these studies, the Investigators propose to advance towards the next stage of this research process: a "screen and treat" strategy. The current trial starts with a Screening phase testing up to 1000 asymptomatic adolescents 14-18 years of age from 3 cities of Chile (Colina, Temuco and Coyhaique), to find a total of 210 persistently-infected participants. Persistently-infected adolescents will be included in a Second phase of this trial: A randomized, case-control, non-blinded study to either receive antimicrobial treatment targeting H. pylori eradication (cases) or no treatment (controls). A subset of 60 non-infected adolescents will be followed-up in matched times. This aims to provide evidence on the effect of treatment on clinical outcomes and serum biomarkers related to gastric damage, as well as composition and antimicrobial resistance of gut microbiota. The Investigators expect that eradication therapy will be successful in \>90% of persistently infected adolescents, with reinfection rates not surpassing 15% in a 2-3 year period, and to be associated with a decrease in clinical findings indicative of gastric disease, and a decrease in serum biomarker indicative of "gastric damage".

Conditions

Helicobacter Pylori Infection

Keywords

Helicobacter pylori; Screen and treat; Pepsinogen; Adolescent

Outcome Measures

Primary Outcomes (3)

• Percentage of persistently-infected teenagers which change UBT status from positive to negative 1 month post-treatment, as compared to non-treated subjects.

  UBT samples will be obtained pre-treatment and 1 month post-treatment.

  a. Baseline: 2 or 3 samples obtained pre-treatment (separated by 30 days) to detect persistently infected children b. One month post-treatment.

• Change in the percentage of persistently-infected adolescents which have "gastric disease" according to gastroenterologist examination from baseline (pre-treatment) to 2-4 months post successful eradication therapy, as compared to non-treated subjects

  Clinical evaluation by gastroenterologist or trained physician, blind to the treatment arm of the subject, for specific GI signs/symptoms, will be performed at baseline (during the month prior to treatment) and posttreatment (2-4 months post treatment). Successful eradication: Negative UBT sample 30 days after treatment

  a. Baseline evaluation during the month prior to treatment. b. 2-4 months post treatment

• Change in blood levels of biomarkers indicative of gastric damage in adolescents with successful eradication after treatment, as compared to non-treated subjects after 6 month follow up.

  Blood samples for Pepsinogen (PG) I, PGII, gastrin and other potential biomarkers of "gastric damage. PGI/PGII/Gastrin-17: will be assessed in serum using GastroPanel® (Biohit Oyj, Helsinki, Finland). Two additional biomarkers of GC will be assessed by ELISA-commercial kits: VCAM-1 and CXCL13. Samples will be collected at baseline, 1 month and 6 months post treatment.

  a. Baseline: Within 2 weeks before initiation of eradication treatment and at similar time-frame in non-treated age matched controls (pre-sample) b. 1 month after treatment c. 6 months post treatment

Secondary Outcomes (2)

• Change in faecal Escherichia coli and Enterococcus antimicrobial resistance rates in treated subjects from baseline to 1 month and 6-12 months post treatment, as compared to non-treated subjects.

  a. Baseline: Within one month before treatment b. 1 month post treatment c. 6-12 months post treatment (and at similar time-frame in non-treated age matched controls)]

• Change in gut microbiome alpha-diversity index in treated subjects from baseline to 1 month and 6-12 months post-treatment, as compared to to non-treated subjects.

  a. Baseline: Within one month before treatment b. 1 month post treatment c. 6-12 months post treatment (and at similar time-frame in non-treated age matched controls)]

Other Outcomes (7)

• Prevalence of H.pylori persistent infection in adolescents in Colina, Temuco and Aysén

  2 or 3 samples obtained pre-treatment (separated by 30 days) to detect persistently infected children

• Effect of treatment on frequency of clarithromycin resistance comparing those subject who would not eradicate with non-treated individuals

  a. Baseline: Within 1 month before eradication b.Within 6 months after the positive UBT sample indicating non-eradication or reinfection.

• Overall reinfection rates in adolescents with successful eradication after treatment

  a. One month post treatment to assess successful eradication b. 6 months after treatment c. Every 6 months up to 24 months post treatment

Study Arms (3)

Cases

EXPERIMENTAL

140 children with H. pylori-persistent infection, who will receive eradication therapy

Drug: Lansoprazole; Drug: Amoxicillin; Drug: Clarithromycin; Drug: Metronidazole

Controls

NO INTERVENTION

70 children with H. pylori-persistent infection, who will not receive eradication therapy

Non infected Controls

NO INTERVENTION

60 adolescents with no H. pylori infection, they will not receive eradication therapy

Interventions

Lansoprazole DRUG

14 days of Lansoprazole (30 mg BID) (days 1-14)

Cases

Amoxicillin DRUG

7 days of Amoxicillin (1000 mg BID) (days 1-7)

Cases

Clarithromycin DRUG

7 days of Clarithromycin (500 mg BID) (days 8-14)

Cases

Metronidazole DRUG

7 days of Metronidazole (500 mg BID) (days 8-14)

Cases

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy teenagers 14-18 years of age from Colina, Temuco or Coyhaique
• At least one responsible adult family member accessible for phone contact.
• Persistent H. pylori infection determined by at least 2 positive UBT tests in a 3 months period (except for Non-infected Controls)

You may not qualify if:

• Teenagers not consenting to treatment will be invited to continue as non-treated controls.
• Known allergy to any of the antimicrobials used in the trial protocol (except for Non-infected Controls)
• Signs/symptoms compatible with organic abdominal pain according to Rome IV criteria: persistent right upper or right lower quadrant pain, dysphagia, odynophagia, persistent vomiting, gastrointestinal blood loss, involuntary weight loss, deceleration of linear growth, delayed puberty.
• Prior eradication therapy
• Antimicrobial course received during the previous month (at least 3 days of treatment at appropriate dosing, children meeting this criteria can be included at a later stage)
• Pregnancy
• Use of immunosuppressive or biologic drugs
• Children deemed "not healthy" after review of the questionnaire by study physician

Sponsors & Collaborators

• Miguel O'Ryan Gallardo: lead
• Fondo Nacional de Desarrollo Científico y Tecnológico, Chile: collaborator

Study Sites (3)

Universidad de Aysén

Coyhaique, Chile

RECRUITING

Universidad de Chile

Santiago, Chile

RECRUITING

Universidad de la Frontera

Temuco, Chile

RECRUITING

Related Publications (5)

• O'Ryan ML, Lucero Y, Rabello M, Mamani N, Salinas AM, Pena A, Torres-Torreti JP, Mejias A, Ramilo O, Suarez N, Reynolds HE, Orellana A, Lagomarcino AJ. Persistent and transient Helicobacter pylori infections in early childhood. Clin Infect Dis. 2015 Jul 15;61(2):211-8. doi: 10.1093/cid/civ256. Epub 2015 Apr 2.

  PMID: 25838286 BACKGROUND

• O'Ryan ML, Rabello M, Cortes H, Lucero Y, Pena A, Torres JP. Dynamics of Helicobacter pylori detection in stools during the first 5 years of life in Chile, a rapidly developing country. Pediatr Infect Dis J. 2013 Feb;32(2):99-103. doi: 10.1097/INF.0b013e318278b929.

  PMID: 23076385 BACKGROUND

• Lucero Y, Lagomarcino AJ, Torres JP, Roessler P, Mamani N, George S, Huerta N, Gonzalez M, O'Ryan M. Helicobacter pylori, clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage in healthy school-aged children: A case-control study. Int J Infect Dis. 2021 Feb;103:423-430. doi: 10.1016/j.ijid.2020.11.202. Epub 2020 Dec 2.

  PMID: 33278617 BACKGROUND

• Lucero Y, Lagomarcino AJ, Torres JP, Roessler P, Mamani N, George SA, Huerta N, Gonzalez M, O'Ryan G M. Effect of Helicobacter pylori eradication therapy on clinical and laboratory biomarkers associated with gastric damage in healthy school-aged children: A randomized non-blinded trial. Helicobacter. 2021 Dec;26(6):e12853. doi: 10.1111/hel.12853. Epub 2021 Sep 15.

  PMID: 34528337 BACKGROUND

• George S, Lucero Y, Cabrera C, Zabala Torres B, Fernandez L, Mamani N, Lagomarcino A, Aguilera X, O'Ryan M. Protocol for a randomised 'screen-and-treat' Helicobacter pylori eradication trial in 14-18-years-old adolescents residing in three regions of Chile: effectiveness and microbiological host implications. BMJ Open. 2025 Jan 30;15(1):e084984. doi: 10.1136/bmjopen-2024-084984.

  PMID: 39890135 DERIVED

MeSH Terms

Interventions

Lansoprazole; Amoxicillin; Clarithromycin; Metronidazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Erythromycin; Macrolides; Polyketides; Lactones; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles

Study Officials

• Miguel O'Ryan, MD

  University of Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yalda Lucero, MD, PhD

CONTACT

+56229786658; ylucero@uchile.cl

Sergio George, MD, PhD

CONTACT

+56225756103; sgeorge@ug.uchile.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded Gastroenterologist or trained physician who performs the surveillance after eradication treatment. No other parties will be masked in the clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor, Pediatrician, Infectious Diseases Specialist. Full Professor.

Model Details: Screening phase: 14-18-year-old students (up to 1000) from three cities will be invited. After obtaining informed consent, eligible participants without exclusion criteria will undergo an H. pylori screening test (Urea Breath Test; UBT). Those negative will exit, except for a subset to be followed as a non-infected controls. Subjects with a positive test will undergo two confirmatory tests 30 days apart to confirm infection persistence. Approximately 20-25% are expected to be positive. Intervention phase: those with persistent H. pylori infection will undergo gastroenterological evaluation 1 month before randomization (2:1) to receive antimicrobial treatment or no treatment. Non-infected controls will be followed at matched intervals. If untreated, subjects with persistent infection will be offered the eradication regimen after completing the initial 6-month follow-up with blood and stool samples taken.

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: July 3, 2023
• Study Start: August 2, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 6 months and ending 36 months after the publication of results in a peer-reviewed journal
• Access Criteria: Data will be shared to researchers who provide a methodologically rigorous proposal and an ethics approval for the project. Proposals should be directed to moryan@uchile.cl, ylucero@uchile.cl, and sgeorge@uchile.cl. To gain access, data requestors will need to sign a data access agreement. Data will be sent via email directly to the person requesting the data.

Locations

CL (3)