Clostridioides Difficile Infection: Analyzing CLInic Evolution and Bacterial Clearance

NCT06030245 | Recruiting

• 1 other identifier: DECLIC
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Clostridium Difficile Infections

Outcome Measures

Primary Outcomes (1)

• Duration of delay between diagnosis of CDI and early or late elimination of C. difficile

  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.

  Month 2

Secondary Outcomes (4)

• Confronting digestive microbiota dysbiosis with C. difficile elimination kinetics

  Month 2

• Impact of antibiotics prescribed for the treatment of CDI after 10 days of treatment

  Day 10

• 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

• Evaluation of the colonic and salivary mucosal immune response of included patients, in relation to patient progress and C. difficile elimination kinetics.

  Month 2

Study Arms (1)

Patients with Clostridioides infection

The following procedures are specific to this test: 8 additional stool swabs (or Fecal Swab in the absence of stool output) to that of the initial diagnosis, plus four saliva swabs. Rectal swabs may cause anal irritation. The patient must also complete a stool collection form.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized in a department of Hôpital Paris Saint-Joseph with microbiologically documented Clostridioides difficile infection or microbiologically documented recurrence of Clostridioides difficile infection, for whom treatment of Clostridioides difficile infection is to be initiated.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Study Sites (1)

Fondation Hôpital Saint-Joseph

Paris, 75014, France

RECRUITING

Related Publications (22)

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• Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044. doi: 10.1093/cid/ciab549.

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• Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, Sears P, Gorbach S; OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012 Apr;12(4):281-9. doi: 10.1016/S1473-3099(11)70374-7. Epub 2012 Feb 8.

  PMID: 22321770 BACKGROUND

• Guery B, Menichetti F, Anttila VJ, Adomakoh N, Aguado JM, Bisnauthsing K, Georgopali A, Goldenberg SD, Karas A, Kazeem G, Longshaw C, Palacios-Fabrega JA, Cornely OA, Vehreschild MJGT; EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018 Mar;18(3):296-307. doi: 10.1016/S1473-3099(17)30751-X. Epub 2017 Dec 19.

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• Guery B, Berger P, Gauzit R, Gourdon M, Barbut F; DAFNE study group; Dafne Study Group, Bemer P, Bessede E, Camou F, Cattoir V, Couzigou C, Descamps D, Dinh A, Laurans C, Lavigne JP, Lechiche C, Leflon-Guibout V, Le Monnier A, Levast M, Mootien JY, N'Guyen Y, Piroth L, Prazuck T, Rogeaux O, Roux AL, Vachee A, Vernet Garnier V, Wallet F. A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France. J Int Med Res. 2021 Jun;49(6):3000605211021278. doi: 10.1177/03000605211021278.

  PMID: 34162264 BACKGROUND

• Watt M, Dinh A, Le Monnier A, Tilleul P. Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France. J Med Econ. 2017 Jul;20(7):678-686. doi: 10.1080/13696998.2017.1302946. Epub 2017 Mar 16.

  PMID: 28299963 BACKGROUND

• Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001 Jan 20;357(9251):189-93. doi: 10.1016/S0140-6736(00)03592-3.

  PMID: 11213096 BACKGROUND

• Chilton CH, Crowther GS, Todhunter SL, Ashwin H, Longshaw CM, Karas A, Wilcox MH. Efficacy of alternative fidaxomicin dosing regimens for treatment of simulated Clostridium difficile infection in an in vitro human gut model. J Antimicrob Chemother. 2015 Sep;70(9):2598-607. doi: 10.1093/jac/dkv156. Epub 2015 Jun 14.

  PMID: 26078392 BACKGROUND

• Le Monnier A, Candela T, Mizrahi A, Bille E, Bourgeois-Nicolaos N, Cattoir V, Farfour E, Grall I, Lecointe D, Limelette A, Marcade G, Poilane I, Poupy P, Kansau I, Zahar JR, Pilmis B; GMC Group. One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals. J Hosp Infect. 2022 Nov;129:65-74. doi: 10.1016/j.jhin.2022.05.011. Epub 2022 May 28.

  PMID: 35640734 BACKGROUND

• Le Monnier A, Duburcq A, Zahar JR, Corvec S, Guillard T, Cattoir V, Woerther PL, Fihman V, Lalande V, Jacquier H, Mizrahi A, Farfour E, Morand P, Marcade G, Coulomb S, Torreton E, Fagnani F, Barbut F; GMC Study Group. Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals. J Hosp Infect. 2015 Oct;91(2):117-22. doi: 10.1016/j.jhin.2015.06.017. Epub 2015 Jul 22.

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• Meza-Torres J, Auria E, Dupuy B, Tremblay YDN. Wolf in Sheep's Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections. Microorganisms. 2021 Sep 10;9(9):1922. doi: 10.3390/microorganisms9091922.

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• Barbut F, Galperine T, Vanhems P, Le Monnier A, Durand-Gasselin B, Canis F, Jeanbat V, Duburcq A, Alami S, Bensoussan C, Fagnani F. Quality of life and utility decrement associated with Clostridium difficile infection in a French hospital setting. Health Qual Life Outcomes. 2019 Jan 11;17(1):6. doi: 10.1186/s12955-019-1081-5.

  PMID: 30634997 BACKGROUND

• Debast SB, Bauer MP, Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014 Mar;20 Suppl 2:1-26. doi: 10.1111/1469-0691.12418.

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Related Links

• Clostridioides difficile infection: guidance on management and treatment \[Internet\]. GOV.UK. 2022

Biospecimen

Retention: SAMPLES WITHOUT DNA

additional stool samples (or Fecal Swab in the absence of stool output) to that of the initial diagnosis, as well as saliva samples

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Assaf MIZRAHI, MD

  Fondation Hôpital Saint-Joseph

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Assaf MIZRAHI, MD

CONTACT

144127030; amizrahi@ghpsj.fr

Helene BEAUSSIER, PharmD, PhD

CONTACT

144127883; crc@ghpsj.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 8, 2023
• Study Start: September 18, 2023
• Primary Completion (Estimated): November 17, 2026
• Study Completion (Estimated): January 17, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

FR (1)