Clostridioides Difficile Infection: Analyzing CLInic Evolution and Bacterial Clearance

Recruiting

• Conditions: Clostridium Difficile Infections

• Registration Number: NCT06030245
• Lead Sponsor: Fondation Hôpital Saint-Joseph

Brief Summary

Clostridioides difficile (formerly Clostridium) is a bacterium found in the form of spores (resistance form) in the environment to which patients may be exposed. This bacterium used to belong to the Clostridium genus, but analysis of its 16S ribosomal RNA in 2016 led to its being distinguished from it. Once the spore has been ingested, it can germinate in vegetative form (the active form of the bacterium), taking on the appearance of a Gram-positive bacillus that will colonize the digestive microbiota. This preliminary stage of digestive colonization by the bacteria is facilitated by certain factors, notably nasogastric probing, antacids, etc. Antibiotics, for their part, disrupt the bacteria of the digestive microbiota (dysbiosis), thus facilitating the implantation of C. difficile. Certain strains (known as toxigenic) will produce the main virulence factors: toxins A (TcdA) and B (TcdB) ± a third toxin (binary toxin or CDT), and thus cause the main clinical signs of digestive infection, particularly in patients with risk factors for C. difficile infection (progressive cancer, immunodepression, etc.).

Clostridioides difficile infection (CDI) is characterized by variable clinical presentations, ranging from simple watery diarrhea without colitis, which often resolves spontaneously, to severe forms with complications such as pseudomembranous colitis, intestinal perforation or septic shock, which have a very poor prognosis.

Management of this type of CDI relies mainly on the oral administration of anti-clostridium difficile antibiotics such as fidaxomicin (FDX) or vancomycin (VAN) for 10 days, as recommended by the European ESCMID, British and American IDSA guidelines. Oral metronidazole is recommended only in the absence of availability of the first two molecules (community use). Despite this treatment, one of the main characteristics of CDI is a high recurrence rate, which can reach 25% of cases. With FDX, recurrence rates appear to be lower, especially as its administration regimen is optimized. Nevertheless, its high cost is a barrier to its wider use.

In view of the high cost to the community of treating recurrences, and the reduced quality of life of patients suffering from these recurrences, which are sometimes multiple and highly incapacitating, reducing the occurrence of recurrences is a major challenge. A better understanding of the factors leading to recurrence is therefore a prerequisite for optimizing CDI prevention and treatment strategies.

The study of colonic mucosal immunity (aimed at quantifying IgA in stools) could also contribute to a better understanding of patient progress.

All these issues surrounding CDI and its management justify the setting up of a prospective cohort for the longitudinal follow-up of infected patients, enabling us to study the digestive clearance of the bacteria according to various factors, notably the digestive microbiota and the mucosal immune response.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-31
• Study First Submitted QC: 2023-08-31
• Study First Posted: 2023-09-08
• Study Start: 2023-09-18
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-27
• Last Update Posted: 2023-11-28
• Primary Completion: 2025-09-17
• Study Completion: 2025-11-17

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients over 18 years of age
• Patients hospitalized in a department of GH Paris Saint-Joseph with a microbiologically documented Clostridioides difficile infection or a microbiologically documented Clostridioides difficile recurrence.
• Patient to be treated for Clostridioides difficile infection
• French-speaking patient
• Patients who do not object to their participation in the study

Exclusion Criteria

• Patients under guardianship or curatorship
• Patient deprived of liberty
• Patient under court protection
• Pregnant or breast-feeding patient

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Duration of delay between diagnosis of CDI and early or late elimination of C. difficile	Month 2	This outcome corresponds to the kinetics of C. difficile elimination, and the time taken for the various microbiological tests (EIA, immunochromatography (ICT), culturomic and specific qPCR tests) detecting C. difficile in stools to become negative, from the day of diagnosis (i.e. before treatment was started), during the 10-day treatment period and after the end of treatment.

Secondary Outcome Measures

Name	Time	Method
Confronting digestive microbiota dysbiosis with C. difficile elimination kinetics	Month 2	This outcome corresponds to the comparison in terms of number and type of digestive microbiota as a function of C. difficile elimination kinetics before treatment (at the time of diagnosis), at the end of 10 days of CDI treatment and after the end of treatment.
Determination of the form in which C. difficile persists in the digestive microbiota during treatment and after the end of treatment until it is eliminated.	Month 2	This outcome corresponds to the type of the bacterial form (vegetative or spore-forming) that persists during and after ICD treatment by qPCR, Propidium monoazide - qPCR (PMA-qPCR) (viable or dead bacteria) and culturomics until digestive clearance of the bacteria.
Impact of antibiotics prescribed for the treatment of CDI after 10 days of treatment	Day 10	This outcome corresponds to the comparison in terms of number and type of diversity of digestive microbiota according to the type of anti-C. difficile antibiotic prescribed at the end of treatment, compared with the number and type of digestive observed at the time of diagnosis, i.e. before the start of treatment.
Evaluation of the colonic and salivary mucosal immune response of included patients, in relation to patient progress and C. difficile elimination kinetics.	Month 2	This outcome corresponds to the number of participants with a development of a C. difficile anti-toxin IgA response and correlation of colonic/salivary IgA levels after ICD with patient course (single, recurrent and severe forms) and C. difficile elimination kinetics.

Trial Locations

Locations (1)

Fondation Hôpital Saint-Joseph; 🇫🇷 Paris, France