Fecal Filtrate as a Treatment Option of Multiple Recurrent Clostridioides Difficile Infection (FILTRATE)
Primary Purpose
Clostridium Difficile Infection, Recurrent Clostridium Difficile Infection
Status
Not yet recruiting
Phase
Phase 3
Locations
Hungary
Study Type
Interventional
Intervention
Fecal filtrate transplantation
Conventional fecal microbiota transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile Infection focused on measuring fecal microbiota transplantation, fecal filtrate, recurrent infection
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
Sites / Locations
- Institute for Translational Medicine, University of Pécs
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Fecal filtrate transplantation
Conventional fecal microbiota transplantation
Arm Description
Patients randomized to the fecal filtrate transplantation group
Patients randomized to the conventional fecal microbiota transplantation group
Outcomes
Primary Outcome Measures
Resolution of diarrhea
Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups.
Secondary Outcome Measures
Resolution of diarrhea
Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups.
Recurrence of CDI symptoms
Recurrence of the CDI symptoms (diarrhea, abdominal pain ect.) within 8 weeks after an initial amelioration. The rate of the outcome will be compared within groups.
Overall mortality
Overall mortality. The rate of the outcome will be compared within groups.
Disease associated mortality
Disease-associated mortality. The rate of the outcome will be compared within groups.
Adverse events
Proportion of adverse events (AE) and serious adverse events (SAE). The rate of the outcome will be compared within groups.
Change of the intestinal microbiome
Change of the intestinal microbiome at the end of the follow up period regarding to the initial intestinal microbiome. The rate of the outcome will be compared within groups.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04960306
Brief Title
Fecal Filtrate as a Treatment Option of Multiple Recurrent Clostridioides Difficile Infection
Acronym
FILTRATE
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pecs
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection, Recurrent Clostridium Difficile Infection
Keywords
fecal microbiota transplantation, fecal filtrate, recurrent infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
238 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fecal filtrate transplantation
Arm Type
Active Comparator
Arm Description
Patients randomized to the fecal filtrate transplantation group
Arm Title
Conventional fecal microbiota transplantation
Arm Type
Active Comparator
Arm Description
Patients randomized to the conventional fecal microbiota transplantation group
Intervention Type
Biological
Intervention Name(s)
Fecal filtrate transplantation
Intervention Description
Patients will receive 5-8 encapsulated lyophilized fecal filtrate transplantations in enterosolvent, size "0" capsules. Before intervention patients will receive proton pump inhibitors and prokinetics. After the preparation, the participants will be instructed to swallow the capsules one by one within 5 minutes with fluid to help to swallow the capsules.
Intervention Type
Biological
Intervention Name(s)
Conventional fecal microbiota transplantation
Intervention Description
Patients will receive 5-8 encapsulated lyophilized conventional fecal microbiota transplantations in enterosolvent, size "0" capsules. Before intervention patients will receive proton pump inhibitors and prokinetics. After the preparation, the participants will be instructed to swallow the capsules one by one within 5 minutes with fluid to help to swallow the capsules.
Primary Outcome Measure Information:
Title
Resolution of diarrhea
Description
Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Resolution of diarrhea
Description
Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups.
Time Frame
1 year
Title
Recurrence of CDI symptoms
Description
Recurrence of the CDI symptoms (diarrhea, abdominal pain ect.) within 8 weeks after an initial amelioration. The rate of the outcome will be compared within groups.
Time Frame
8 weeks, 1 year
Title
Overall mortality
Description
Overall mortality. The rate of the outcome will be compared within groups.
Time Frame
8 weeks, 1 year
Title
Disease associated mortality
Description
Disease-associated mortality. The rate of the outcome will be compared within groups.
Time Frame
8 weeks, 1 year
Title
Adverse events
Description
Proportion of adverse events (AE) and serious adverse events (SAE). The rate of the outcome will be compared within groups.
Time Frame
8 weeks, 1 year
Title
Change of the intestinal microbiome
Description
Change of the intestinal microbiome at the end of the follow up period regarding to the initial intestinal microbiome. The rate of the outcome will be compared within groups.
Time Frame
8 weeks, 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Péter Hegyi, MD,PhD, Dsc
Phone
+3672/536-246
Email
p.hegyi@tm-centre.org
Facility Information:
Facility Name
Institute for Translational Medicine, University of Pécs
City
Pécs
ZIP/Postal Code
7624
Country
Hungary
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Péter Hegyi, MD,PhD, Dsc
Email
p.hegyi@tm-centre.org
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34150673
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.
Results Reference
result
PubMed Identifier
33106983
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.
Results Reference
result
PubMed Identifier
24762631
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.
Results Reference
result
Links:
URL
https://tm-centre.org/en/research/
Description
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Fecal Filtrate as a Treatment Option of Multiple Recurrent Clostridioides Difficile Infection
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