None listed
Conditions
Brief summary
Background: Clostridioides difficile infection is the commonest cause of drug treatment-induced infectious diarrhea, which is often recurrent with high mortality. Current treatments mainly include antibiotics, which have low sustained cure rates of 30-35%. Therefore, alternative or additive treatments are required. Hypothesis: In the treatment of the first recurrent or refractory Clostridioides difficile infection, FMT alone leads to a greater sustained cure rate than oral vancomycin hydrochloride treatment alone but to a comparable rate to vancomycin hydrochloride plus FMT combination. Design: Randomized controlled trial that will allocate participants in a 1:1:1 ratio to one of three groups: (1) FMT alone, (2) vancomycin alone, and (3) vancomycin followed by FMT. Groups 1 and 2 will be double-blinded because these are the primary outcome comparison groups. Group 3 will remain unblinded because the treatment days differ, and there is no justifiable reason to blind them. Participants: Eighty-four people aged 16-90 diagnosed with recurrent or refractory Clostridioides difficile infection who can swallow capsules. Donors: Eight healthy donors aged 16-40 years who pass a strict screening process. Interventions: FMT capsules vs vancomycin hydrochloride capsules vs vancomycin hydrochloride capsules, followed by FMT. Assessments: Data on treatment response, gut symptoms and composition, well-being, quality of life and safety will be collected over 12-weeks. Assessment measures include a clinical evaluation, the Bristol Stool Chart, the Gastrointestinal Symptom Rating Scale (GSRS), the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS) and the the EQ-5D-5L.. The stool microbiome from donors and participants (baseline and 12 weeks after treatment) will be characterized by metagenomic sequencing.
Interventions
Arm 1: FMT alone
Participants in this group will be randomly assigned to receive 20 FMT capsules over two consecutive days (days 1-2) in the morning. In addition, they will take one placebo-vancomycin capsule containing 125 mg of maltodextrin four times per day for 10 consecutive days (days 1-10). This group will remain blinded to the treatment allocation.
The FMT capsules contain concentrated gut microbiota provided by carefully screened healthy donors. The microbiota is suspended in a cryop
Arm 1: FMT alone Participants in this group will be randomly assigned to receive 20 FMT capsules over two consecutive days (days 1-2) in the morning. In addition, they will take one placebo-vancomycin capsule containing 125 mg of maltodextrin four times per day for 10 consecutive days (days 1-10). This group will remain blinded to the treatment allocation. The FMT capsules contain concentrated gut microbiota provided by carefully screened healthy donors. The microbiota is suspended in a cryoprotective solution consisting of 15% glycerol and 0.9% saline at a concentration of 0.5 g per milliliter. The suspension is then double-encapsulated in sizes 0 and 0 delayed-release capsules (DRcapsTM, Capsugel, Australia) in 0.5 ml aliquots. The placebo-vancomycin capsules contain 125 mg of maltodextrin. To ensure that participants adhere to the treatment and to monitor their safety, a registered nurse will supervise the administration of FMT capsules and observe for any side effects. Adherence to the FMT-placebo treatment will be monitored through text messages and phone calls. All relevant data will be recorded using the RedCap system.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
16 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Study participants (recipients) will have to meet the following inclusion criteria: 1. Aged 16 to 90 years; AND 2. Ability to swallow all treatment capsules; AND 3. Having: a. First episode Clostridioides difficile infection; OR b. First Recurrent Clostridioides difficile infection; OR c. Refractory Clostridioides difficile infection.
Exclusion criteria
As a real-world trial examining FMT effectiveness, there will be minimal exclusion criteria. However, patients meeting the three below will be excluded: 1. Current systemic antibiotic treatment except if prescribed for Clostridioides difficile infection 2. Severe allergy to foods and/or common medications 3. Current hospitalisation because of severe Clostridioides difficile infection, defined as having at least one of the following that is not directly attributable to a non-clostridioides difficile infection illness (e.g., infection): a. Fever (core body temperature of greater than 38.5°C); b. Marked leukocytosis (leucocyte count greater than 15 x109/L); c. Serum creatinine rise greater than 50% above baseline or if no baseline available greater than 50% above the upper limit of the age-specific reference range;
Outcome results
None listed