Lyophilized Fecal Microbiome Transfer Versus Vancomycin Monotherapy for Primary Clostridioides Difficile Infection in Adults (DONATE)

• Status: Not yet recruiting
• Trial end date: 2025-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical trial is to test whether lyophilized fecal microbime transfer - a dried extract of bacteria from the stool of healthy donors - is better than antibiotic therapy only for treating primary clostridioides difficile infection (CDI) in adult participants.

The main question it aims to answer is whether lyophilized fecal microbiome transfer lowers the number of episodes of CDI compared to antibiotic therapy.

Participants will be assigned to one of two groups:

• In the intervention group participants will be given vancomycin by mouth for five days followed by 5 days of capsules of lyophilized fecal microbiome to swallow, up until day 10.

• In the control group participants will be given vancomycin by mouth for ten days.

• All participants will be asked to arrive for two follow-up visits and to fill out questionnaires. In addition, all participants will be asked to give stool samples before antibiotic therapy and on the two follow-up visits.

Researchers will compare the intervention group and the control group to see if there is a difference in symptoms degree after ten days and in recurrence of the infection after two months. They will also compare side effects, the total use of antibiotics and the change in the composition of bacteria in the stool, namely the presence of bacteria that are resistant to many drugs.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rambam Health Care Campus
• Collaborators: European Institute of Oncology; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Imperial College London; Lithuanian University of Health Sciences; University of Alberta; University of Debrecen
• Treatments: Vancomycin

Criteria

Inclusion Criteria:

• Consenting adults ≥18 years old

• Non-fulminant primary CDI - Primary CDI (pCDI) will be defined as the patient's first event of CDI in the last 3 months presenting with a 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. Both non-severe and severe patients will be included.

Exclusion Criteria:

• Patients who cannot provide informed consent and do not have a legal guardian;

• 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;

• Ileus or toxic megacolon;

• Life-threatening or fulminant CDI (white blood cell count >30,000 cells/mL; temperature >40°C; evidence of hypotension [systolic blood pressure <90 mmHg], septic shock, peritoneal signs, or significant dehydration);

• Inpatients with early fulminant CDI, defined as patients showing progression despite treatment with a sequential organ failure assessment score (SOFA score) ≥ 4 due to CDI 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, having blood drawn, and providing 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.