Feasibility and Performance of FFPE qPCR for Detection of Clarithromycin Resistance in Helicobacter Pylori (HED-2T)
Feasibility and Performance of qPCR on Formalin-Fixed, Paraffin-Embedded Gastric Biopsies for Detection of Clarithromycin Resistance in Helicobacter Pylori in Routine Clinical Practice
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Helicobacter pylori (H. pylori) infection is a common chronic bacterial infection associated with peptic ulcer disease and gastric malignancies. Clarithromycin resistance is an important cause of treatment failure. Current recommendations support susceptibility-guided treatment based on the detection of clarithromycin resistance; however, in routine clinical practice, resistance testing remains infrequently performed.
This prospective, single-center observational study will evaluate the feasibility and diagnostic performance of real-time polymerase chain reaction (qPCR) performed on formalin-fixed, paraffin-embedded (FFPE) gastric biopsies collected during routine gastroscopy. The study will investigate whether FFPE tissue samples already obtained for histopathological examination can be used to detect H. pylori and mutations in the 23S rRNA gene associated with clarithromycin resistance.
Participants will be adults with suspected H. pylori infection who require gastric biopsies during gastroscopy. H. pylori infection will be confirmed by histological examination and immunohistochemistry. For participants with confirmed H. pylori infection, corresponding FFPE tissue blocks will be selected for DNA extraction and qPCR targeting mutations associated with clarithromycin resistance.
The primary objective is to prospectively evaluate the feasibility and performance of qPCR on FFPE gastric biopsies for the detection of clarithromycin resistance in H. pylori in routine clinical practice. Diagnostic performance will include sensitivity and specificity for H. pylori detection and for detection of clarithromycin-resistance mutations, as well as the proportion of samples yielding exploitable results and the time required to obtain results.
Secondary objectives include describing the prevalence and epidemiology of clarithromycin-resistance mutations in the study population; assessing concordance between FFPE qPCR and immunohistochemistry, particularly in cases with low bacterial load; assessing concordance between FFPE qPCR and bacteriological PCR; evaluating the potential impact of qPCR results on therapeutic management; and assessing the medical-economic impact of a clarithromycin-resistance screening strategy based on FFPE qPCR compared with empirical treatment and bacteriological PCR.
The study will include approximately 250 participants. The study is prospective and monocentric and does not involve any modification of the patient's usual clinical management. Gastric biopsies will be collected during routine gastroscopy and analyzed by pathology and bacteriology according to the study protocol. The planned inclusion period is July 2026 to January 2027, with a 10-day follow-up period.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Bouchra BENKESSOU
- Phone Number: 07 64 48 60 16
- Email: b.benkessou@hexagone-sante-paris.fr
Study Locations
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Paris, France, 75016
- Benkessou
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Contact:
- BOUCHRA benkessou
- Phone Number: 0764486016
- Email: b.benkessou@hexagone-sante-paris.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age ≥18 years.
- Ability to provide non-opposition to participate in the study.
- Participants with suspected Helicobacter pylori infection requiring gastric biopsies during gastroscopy for H. pylori assessment by histopathology and bacteriology, including clarithromycin resistance testing by PCR.
- Confirmed presence of Helicobacter pylori by histological examination and immunohistochemistry.
Exclusion Criteria:
- Minor participants.
- Adults under legal protection, guardianship or curatorship.
- Refusal to participate in the study.
- Recent antibiotic therapy (<4 weeks) that may affect bacterial load.
- Recent proton pump inhibitor treatment (<2 weeks).
- Insufficient tissue quantity for complementary analyses.
- Poor quality fixation or preservation of samples.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Diagnostic performance of q-PCR on FFPE gastric biopsies for detection of Helicobacter pylori clarithromycin resistance
Time Frame: Within 10 days after gastric biopsy collection
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Sensitivity and specificity of q-PCR performed on formalin-fixed paraffin-embedded (FFPE) gastric biopsies for: detection of Helicobacter pylori infection (using immunohistochemistry and internal PCR positive control as reference); detection of clarithromycin resistance-associated mutations (23S rRNA gene mutations); assessment of the proportion of exploitable samples (technical success rate); turnaround time for obtaining results.Sensitivity and specificity of q-PCR performed on formalin-fixed paraffin-embedded (FFPE) gastric biopsies for: detection of Helicobacter pylori infection (using immunohistochemistry and internal PCR positive control as reference); detection of clarithromycin resistance-associated mutations (23S rRNA gene mutations); assessment of the proportion of exploitable samples (technical success rate); turnaround time for obtaining results. |
Within 10 days after gastric biopsy collection
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Prevalence of clarithromycin resistance in Helicobacter pylori infection
Time Frame: Within 10 days after gastric biopsy collection
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Prevalence of clarithromycin resistance-associated mutations according to age, sex, clinical indication and clinical setting.
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Within 10 days after gastric biopsy collection
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Concordance between q-PCR FFPE and immunohistochemistry results
Time Frame: Within 15 days after gastric biopsy collection
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Agreement between q-PCR performed on FFPE gastric biopsies and immunohistochemistry results, particularly in cases with low bacterial load.
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Within 15 days after gastric biopsy collection
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Concordance between q-PCR FFPE and bacteriological PCR results
Time Frame: Within 15 days after gastric biopsy collection
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Agreement between q-PCR performed on FFPE gastric biopsies and reference PCR performed on bacteriological samples (and culture when available).
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Within 15 days after gastric biopsy collection
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Impact of q-PCR results on therapeutic management
Time Frame: Within 15 days after inclusion and availability of laboratory results
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Proportion of participants whose treatment strategy is modified based on q-PCR results, including prescription of a treatment guided by clarithromycin susceptibility profile.
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Within 15 days after inclusion and availability of laboratory results
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Medical-economic impact of q-PCR FFPE strategy
Time Frame: Through study completion, an average of 12 months
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Comparison of costs between q-PCR FFPE strategy and current empirical or bacteriological PCR-based strategies, including cost per adapted treatment and cost per avoided therapeutic failure.
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Through study completion, an average of 12 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dr Michaël Lévy, Clinique Bizet
Publications and helpful links
General Publications
- Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 11;71(9):1724-1762. doi: 10.1136/gutjnl-2022-327745.
- Nezami BG, Jani M, Alouani D, Rhoads DD, Sadri N. Helicobacter pylori Mutations Detected by Next-Generation Sequencing in Formalin-Fixed, Paraffin-Embedded Gastric Biopsy Specimens Are Associated with Treatment Failure. J Clin Microbiol. 2019 Jun 25;57(7):e01834-18. doi: 10.1128/JCM.01834-18. Print 2019 Jul.
- Schmitt BH, Regner M, Mangold KA, Thomson RB Jr, Kaul KL. PCR detection of clarithromycin-susceptible and -resistant Helicobacter pylori from formalin-fixed, paraffin-embedded gastric biopsies. Mod Pathol. 2013 Sep;26(9):1222-7. doi: 10.1038/modpathol.2013.48. Epub 2013 Apr 12.
- Oleastro M, Menard A, Santos A, Lamouliatte H, Monteiro L, Barthelemy P, Megraud F. Real-time PCR assay for rapid and accurate detection of point mutations conferring resistance to clarithromycin in Helicobacter pylori. J Clin Microbiol. 2003 Jan;41(1):397-402. doi: 10.1128/JCM.41.1.397-402.2003.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2026-A01143-48 (Other Identifier: ID-RCB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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