NCT05266807.

Study name	Fecal microbiota transplantation versus vancomycin or fidaxomicin in Clostridioides difficile infection first recurrence (FENDER)
Methods	Open‐label, randomized controlled trial
Participants	Inclusion criteria Adults aged ≥ 18 years at time of informed consent Informed consent signature Medical record documentation of first recurrence of CDI defined as: previous episode of treated and cured CDI within last 8 weeks confirmed by medical record documentation of a clinical picture of CDI combined with a CDI test performed according to CDI diagnosis ESCMID guidelines current combination of CDI signs and symptoms, confirmed by medical record documentation of microbiologic evidence of C difficile toxin and C difficile in stools shown by a CDI test performed according to CDI diagnosis ESCMID guidelines, with a mandatory toxin A/B EIA positive test and without reasonable evidence of another cause of diarrhea No multiple episodes (> 1 recurrence) of CDI that occurred within 3 previous months Already taking since < 10 days or will start a course of antibiotics (vancomycin or fidaxomicin) to control recurrent CDI symptoms at the time of screening Willing and able to have FMT by capsule Exclusion criteria Complicated CDI (≥ 1 of the following signs or symptoms related to CDI: hypotension requiring vasopressors, ICU admission for a complication of CDI, ileus leading to placement of nasogastric tube, toxic megacolon, colonic perforation, colectomy, or colostomy) Prior FMT within 6 months of randomization Prior colectomy, colostomy, ileostomy, or gastrectomy Metronidazole already given for treatment of first rCDI for > 3 days Need for continued non‐anti‐CDI systemic antibiotics Anticipated indication for antibiotics treatment (for a non‐CDI reason) in next 8 weeks Other infectious causes of diarrhea beyond CDI Inflammatory bowel disease Swallowing disorders, Zenker diverticulum, gastroparesis, or prior small bowel obstruction Known hypersensitivity to vancomycin or fidaxomicin Pregnant/lactating women Estimated life expectancy < 10 weeks Inability to follow protocol study procedures Inability to give informed consent Any condition or medications that will put the participant at greater risk from FMT according to the investigator Severely immunocompromised
Interventions	Intervention Vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per standard of care for 10 days, followed 24 hours later by 1 oral FMT (15 capsules administered at day 1 and 15 capsules at day 2), and a second oral FMT depending on recurrent CDI severity Comparison Vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per standard of care for 10 days
Outcomes	Primary outcome Sustained clinical cure rate. Absence of CDI recurrence (time frame: 8 weeks after study treatment completion) Secondary outcomes Treatment failure: early and late CDI recurrence rate (time frame: before 4 weeks and at 5–8 weeks after study treatment completion) CDI new occurrence rate (time frame: between 8 weeks and 12 months after study treatment completion) Long‐term clinical cure (time frame: 6 and 12 months after study treatment completion) Recurrence‐free survival rate from study intervention to CDI recurrence (time frame: 12 months after study treatment completion) Overall survival from study intervention to death (time frame: 12 months after study treatment completion Health status EQ‐5D‐5L measure using 5‐digit code (score from 1 to 5 for each digit, 1 representing no problem and 5 representing worse problem) (mobility, self‐care, usual activities, pain/discomfort, anxiety/depression) (time frame: baseline, 8 weeks, 6 and 12 months after study treatment completion) Health status EQ‐5D‐5L measure using EQ visual analog scale score (0 representing the worst health you can imagine to 100 representing the best health you can imagine) (participant's perception of overall health) (time frame: baseline, 8 weeks, 6 and 12 months after study treatment completion)
Starting date	March 2022
Contact information	Benoit Guery MD, Principal Investigator, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Notes	No results posted

ANC: absolute neutrophil count; CD: Clostridioides difficile; CDI: Clostridioides difficile infection; CTCAE V5.0: Common Terminology Criteria for Adverse Events Version 5.0; EIA: enzyme immunoassay; ESCMID: European Society of Clinical Microbiology and Infectious Diseases; FMT: fecal microbiota transplantation; GI: gastrointestinal; ICU: intensive care unit; PCR: polymerase chain reaction; RBT: rectal bacteriotherapy; rCDI: recurrent Clostridioides difficile infection; WBC: white blood cell count.