Clinical trial NCT04960306: Fecal Filtrate as a Treatment Option of Multiple Recurrent Clostridioides Difficile Infection
Official title: Fecal Filtrate Versus Conventional Microbiota Transplantation in the Treatment of Multiple Recurrent Clostridioides Difficile Infection (FILTRATE): A Protocol of a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Clostridium Difficile Infection
Recurrent Clostridium Difficile Infection
Keywords: fecal microbiota transplantation
fecal filtrate
recurrent infection
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2021-07-13
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clostridioides difficile infection (CDI) is one of the most common hospital-acquired infectious diseases with a high mortality rate (6-30%). The treatment of CDI, especially the recurrent form of the disease is still considered a challenge. The FILTRATE randomized controlled trial aims to investigate the safety and efficacy of fecal filtrate transplantation in the treatment of recurrent CDI and compare it with conventional fecal microbiota transplantation (FMT).

Detailed description: The treatment of recurrent CDI is still a burden on the healthcare system. FMT is highly effective for the treatment of recurrent CDI, resulting in the resolution of CDI up to 100% of the cases. FMT also has a good short-term safety profile, however long-term events like transfer of multiresistant bacteria and other living microorganism is still a major problem. On the other hand, the fecal filtrate contains only bacterial debris, proteins, and antimicrobial compounds and not intact microorganisms.

The FILTRATE trial is a multicenter, two-arm randomized controlled trial, and aims to compare the safety and efficacy of fecal filtrate transplantation to conventional fecal microbiota transplantation (FMT) in the treatment of recurrent CDI. Adult patients with multiple recurrent (\>1) CDIs will be randomized 1:1 to receive either FMT or fecal filtrate transplantation. The transplantation will be carried out using lyophilized capsule on each arm. The primary endpoint of the study will be the clinical resolution of CDI-associated diarrhea 8 weeks after the interventions. Questionnaires will be completed on enrollment and at the time of each follow-up. Adverse events will be recorded and reported to the relevant institutional and national ethics committee. After the intervention, a one-year follow-up is also planned. Blood and stool samples will be collected at baseline and at each follow-up.

Eligibility criteria: Inclusion Criteria:

* age ≥18 years
* multiple recurrent CDI (≥2 previous episodes of CDI)
* at least 3 or more loose or watery stools (Bristol 5-7) per day
* a positive Glutamate Dehydrogenase (GDH)-enzyme and positive CDI toxin A and/or B test
* the patient or the legal guardian sign the written informed consent

Exclusion Criteria:

* pregnancy or breastfeeding
* ongoing antibiotic treatment
* fulminant CDI
* previous FMT
* immunodeficiency
* need of intensive care
* requirement for vasoactive drugs
* other cause of diarrhea
* inflammatory bowel diseases
* irritable bowel syndrome
* life expectancy shorter than 3 months
* unavailable for follow-up visits

Primary outcomes:
measure: Resolution of diarrhea
timeFrame: 8 weeks
Secondary outcomes:
measure: Resolution of diarrhea
timeFrame: 1 year
measure: Recurrence of CDI symptoms
timeFrame: 8 weeks, 1 year
measure: Overall mortality
timeFrame: 8 weeks, 1 year
measure: Disease associated mortality
timeFrame: 8 weeks, 1 year
measure: Adverse events
timeFrame: 8 weeks, 1 year
measure: Change of the intestinal microbiome
timeFrame: 8 weeks, 1 year
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Institute for Translational Medicine, University of Pécs
Study officials:
References:
citation: Varga A, Kocsis B, Sipos D, Kasa P, Vigvari S, Pal S, Dembrovszky F, Farkas K, Peterfi Z. How to Apply FMT More Effectively, Conveniently and Flexible - A Comparison of FMT Methods. Front Cell Infect Microbiol. 2021 Jun 4;11:657320. doi: 10.3389/fcimb.2021.657320. eCollection 2021.
citation: Dembrovszky F, Gede N, Szakacs Z, Hegyi P, Kiss S, Farkas N, Molnar Z, Imrei M, Dohos D, Peterfi Z. Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis. Infect Dis Ther. 2021 Mar;10(1):201-211. doi: 10.1007/s40121-020-00356-9. Epub 2020 Oct 26.
citation: Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, Alm EJ, Gevers D, Russell GH, Hohmann EL. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis. 2014 Jun;58(11):1515-22. doi: 10.1093/cid/ciu135. Epub 2014 Apr 23.