Lyophilized Fecal Microbiome Transfer vs. Vancomycin Monotherapy for Primary Clostridioides Difficile Infection

NCT05709184 | Recruiting DMC

• 1 other identifier: RMB-0176-22
• Study Type: interventional
• Target: 196
• Locations: 6 countries
• Sites: 6

Brief 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.

Conditions

Clostridioides Difficile Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• CDI recurrence

  The re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive CD stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment

  8 weeks

Secondary Outcomes (6)

• Clinical cure

  10 days

• CDI recurrence in patients who achieved clinical cure

  8 weeks

• Sustained clinical response

  8 weeks

• Serious adverse events

  8 weeks

• Patient reported outcomes (PROs) and preferences

  At baseline and 8 weeks

Other Outcomes (6)

• Time to clinical cure

  up to 10 days

• Time to recurrence

  up to 8 weeks

• Total adverse events rate

  8 weeks

Study Arms (2)

Lyophilized fecal microbiome transfer (Lyo-FMT)

EXPERIMENTAL

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

Combination Product: Lyophilized fecal microbiome transfer

Vancomycin monotherapy

ACTIVE COMPARATOR

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).

Drug: Vancomycin

Interventions

Lyophilized fecal microbiome transfer COMBINATION_PRODUCT

Five days of vancomycin followed by five days of lyophilized fecal microbiome transfer, administered in a loading dose of 15 capsules, and a daily maintenance dose of 10 capsules.

Also known as: FMT

Lyophilized fecal microbiome transfer (Lyo-FMT)

Vancomycin DRUG

Ten days of oral vancomycin 125 mg four times daily

Also known as: CDI antibiotic treatment

Vancomycin monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• European Institute of Oncology: collaborator
• University of Alberta: collaborator
• Imperial College London: collaborator
• University of Debrecen: collaborator
• Lithuanian University of Health Sciences: collaborator

Study Sites (6)

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

Related Publications (15)

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MeSH Terms

Conditions

Clostridium Infections

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Milena Pitashny, MD

CONTACT

972-4-7771108; m_pitashny@rmc.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The primary outcome will be assessed by an observer blinded to study group assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical and Research Microbiome Center

Study Record Dates

• First Submitted: January 24, 2023
• First Posted: February 2, 2023
• Study Start: November 15, 2023
• Primary Completion: November 1, 2025
• Study Completion: March 1, 2026
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); HU (1); LI (1); GB (1); CA (1); IT (1)