Feasibility and Performance of FFPE qPCR for Detection of Clarithromycin Resistance in Helicobacter Pylori (HED-2T)

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.