Comparing lyophilized fecal microbiome transfer to vancomycin for treating Clostridioides difficile infection

Lyophilized Fecal Microbiome Transfer for Primary Clostridioides Difficile Infection (DONATE Study): a Multicenter Randomized Controlled Trial

This study is testing if a new treatment using freeze-dried stool can work better than the usual antibiotic for adults with Clostridioides difficile infection.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 196 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rambam Health Care Campus (Academic / other)
• Locations: 6 sites (Edmonton and 5 other locations)
• Trial ID: NCT05709184 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine if lyophilized fecal microbiome transfer (Lyo-FMT) is more effective than standard vancomycin therapy for treating primary Clostridioides difficile infection (CDI) in adults. Participants will be randomly assigned to receive either a short course of vancomycin followed by Lyo-FMT capsules or vancomycin alone. The study will involve follow-up visits and stool sample collection to assess treatment outcomes. The goal is to evaluate the reduction in CDI episodes with the Lyo-FMT approach compared to traditional antibiotic therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with non-fulminant primary CDI.

Not a fit: Patients with a history of CDI within the last 6 months or those with other chronic gastrointestinal disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients suffering from Clostridioides difficile infection.

How similar studies have performed: Other studies have shown promise with fecal microbiome transfer approaches, suggesting potential success for this novel application.

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.

Where this trial is running

Edmonton and 5 other locations

• University of Alberta — Edmonton, Canada (Recruiting)
• University of Debrecen — Debrecen, Hungary (Not_yet_recruiting)
• Rambam Health Care Campus — Haifa, Israel (Recruiting)
• Gemelly institute Policlinico Universitario Fondazione Agostino Gemelli — Rome, Italy (Not_yet_recruiting)
• Hospital of Lithuania University of Health Sciences Kauno klinikos — Kaunas, Lithuania (Not_yet_recruiting)
• Imperial College of London — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Milena Pitashny, MD

Conditions Clostridioides Difficile Infection; Gut microbiome; Colonization resistance; Fecal microbiome transfer; Lyophilization; Multi-drug resistant organisms