Lyophilized Fecal Microbiome Transfer vs. Vancomycin Monotherapy for Primary Clostridioides Difficile Infection (DONATE)
Clostridioides Difficile Infection
About this trial
This is an interventional treatment trial for Clostridioides Difficile Infection focused on measuring Gut microbiome, Colonization resistance, Fecal microbiome transfer, Lyophilization, Multi-drug resistant organisms, Clostridioides Difficile Infection
Eligibility Criteria
Inclusion Criteria: Consenting adults ≥18 years old with non-fulminant primary CDI. Both non-severe and severe patients will be included. Primary CDI (pCDI) will be defined as the patient's first event of CDI in the past 6 months: New-onset diarrhea (≥3 unformed bowel movements (UBM) per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces. A positive CD stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain. Exclusion Criteria: Patients who cannot provide informed consent and do not have a legal guardian; History of CDI 6 months prior to screening Known presence of other stool pathogens known to cause diarrhea; Patients who cannot swallow; Background diagnosis of inflammatory bowel disease, irritable bowel syndrome (IBS), or any other chronic diarrheal disorder; Active gastrointestinal graft versus host disease (GVHD); Neutropenia <500/ml3; Food allergy leading to anaphylaxis; Prior total colectomy or the presence of a small intestinal stoma; Perforated intestine or intestinal fistula or major abdominal surgery in the last 30 days; Fulminant or life-threatening CDI defined as the occurrence of ileus, septic shock or toxic megacolon. Signs of fulminant disease are: white blood cell count >30,000 cells/mL; temperature >40°C; evidence of hypotension [systolic blood pressure <90 mmHg], peritoneal signs, and significant dehydration; Early fulminant CDI (ICU patients) defined as patients showing progression despite treatment with a sequential organ failure assessment score (SOFA score) ≥ 4 due to CDI (13) at day 2 of treatment (prior to randomization); Patients who receive systemic antibiotics due to other reasons which cannot be stopped until 1 day prior to randomization (day 2 of antibiotic therapy); Patients that were not recruited to the study by day 4 of CDI therapy will be excluded from participation; Patients with <3 months life expectancy; Inability or unwillingness to comply with the study protocol, including ingesting capsules, and providing blood or stool samples as scheduled; Participation in another interventional study; In the opinion of the investigator, inappropriateness for the trial (eg, patients with known hypersensitivity to vancomycin); Pregnancy and breastfeeding.
Sites / Locations
- University of Alberta
- University of Debrecen
- Rambam Health Care Campus
- Gemelly institute Policlinico Universitario Fondazione Agostino Gemelli
- Hospital of Lithuania University of Health Sciences Kauno klinikos
- Imperial College of London
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Lyophilized fecal microbiome transfer (Lyo-FMT)
Vancomycin monotherapy
Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of therapy by the clinical team), followed by a loading dose of oral Lyo-FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each Lyo-FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance
Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization).