Clostridioides Difficile Infection: Analyzing CLInic Evolution and Bacterial Clearance

Clostridium Difficile Infections Clinical Trial

— DECLIC  

Official title:

Clostridioides Difficile Infection: Prospective Cohort Analyzing CLInic Evolution and Bacterial Clearance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06030245
• Other study ID #: DECLIC
• Status: Recruiting
• Start date: September 18, 2023
• Est. completion date: November 17, 2025

Study information

• Verified date: November 2023
• Source: Fondation Hôpital Saint-Joseph
• Contact: Assaf MIZRAHI, MD
• Phone: 144127030
• Email: amizrahi[@]ghpsj.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 17, 2025
• Est. primary completion date: September 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile Infections
• Clostridium Infections
• Communicable Diseases
• Infections

Locations

Country	Name	City	State
France	Fondation Hôpital Saint-Joseph	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Fondation Hôpital Saint-Joseph

Country where clinical trial is conducted

France, 

References & Publications (22)

Ahluwalia B, Magnusson MK, Ohman L. Mucosal immune system of the gastrointestinal tract: maintaining balance between the good and the bad. Scand J Gastroenterol. 2017 Nov;52(11):1185-1193. doi: 10.1080/00365521.2017.1349173. Epub 2017 Jul 12. — View Citation

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. — View Citation

Bridgman SL, Konya T, Azad MB, Guttman DS, Sears MR, Becker AB, Turvey SE, Mandhane PJ, Subbarao P; CHILD Study Investigators; Scott JA, Field CJ, Kozyrskyj AL. High fecal IgA is associated with reduced Clostridium difficile colonization in infants. Microbes Infect. 2016 Sep;18(9):543-9. doi: 10.1016/j.micinf.2016.05.001. Epub 2016 May 24. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000 Feb 10;342(6):390-7. doi: 10.1056/NEJM200002103420604. — View Citation

Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prevot 1938. Anaerobe. 2016 Aug;40:95-9. doi: 10.1016/j.anaerobe.2016.06.008. Epub 2016 Jun 28. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Nibbering B, Gerding DN, Kuijper EJ, Zwittink RD, Smits WK. Host Immune Responses to Clostridioides difficile: Toxins and Beyond. Front Microbiol. 2021 Dec 21;12:804949. doi: 10.3389/fmicb.2021.804949. eCollection 2021. — View Citation

Saha S, Yadav D, Pardi R, Patel R, Khanna S, Pardi D. Kinetics of polymerase chain reaction positivity in patients with Clostridioides difficile infection. Therap Adv Gastroenterol. 2021 Oct 8;14:17562848211050443. doi: 10.1177/17562848211050443. eCollection 2021. — View Citation

Sethi AK, Al-Nassir WN, Nerandzic MM, Bobulsky GS, Donskey CJ. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol. 2010 Jan;31(1):21-7. doi: 10.1086/649016. — View Citation

van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Noren T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ; Guideline Committee of the European Study Group on Clostridioides difficile. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021 Dec;27 Suppl 2:S1-S21. doi: 10.1016/j.cmi.2021.09.038. Epub 2021 Oct 20. — View Citation

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. — View Citation

Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996 May;22(5):813-8. doi: 10.1093/clinids/22.5.813. Erratum In: Clin Infect Dis 1996 Aug;23(2):423. — View Citation

Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, Cornely OA, Rahav G, Bouza E, Lee C, Jenkin G, Jensen W, Kim YS, Yoshida J, Gabryelski L, Pedley A, Eves K, Tipping R, Guris D, Kartsonis N, Dorr MB; MODIFY I and MODIFY II Investigators. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017 Jan 26;376(4):305-317. doi: 10.1056/NEJMoa1602615. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Confronting digestive microbiota dysbiosis with C. difficile elimination kinetics	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.	Month 2
Secondary	Impact of antibiotics prescribed for the treatment of CDI after 10 days of treatment	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.	Day 10
Secondary	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.	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.	Month 2
Secondary	Evaluation of the colonic and salivary mucosal immune response of included patients, in relation to patient progress and C. difficile elimination kinetics.	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.	Month 2

External Links

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