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

Clostridioides Difficile Infection Clinical Trial

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

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

This is a multicenter, transnational randomized controlled trial comparing a short course of vancomycin therapy followed by oral lyophilized fecal microbiome transfer (Lyo-FMT) capsules (intervention group) with standard vancomycin monotherapy (control group), for adults with primary Clostridioides difficile infection (pCDI).

The target population will be adult patients with non-fulminant pCDI in the community/hospital according to the setting at the recruiting center. pCDI will be defined as the patient's first event of CDI in the last 6 months presenting with a new-onset diarrhea (≥3 unformed bowel movements per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces. A positive C. difficile 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.

Consenting patients will be randomly assigned to one of two treatment modalities: vancomycin followed by oral lyophilized FMT capsules (intervention group) or vancomycin monotherapy group.

• Lyo-FMT group (intervention group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of antibiotic therapy by the clinical team), followed by a loading dose of oral lyophilized 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 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.

• Antibiotic monotherapy group (control group) - 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).

If symptoms persist on day 10 from the initiation of therapy, further treatment will be given according to study group allocation. In the Lyo-FMT group, FMT will be repeated in the form of 15 FMT capsules per course as clinically indicated. If no resolution of symptoms will be documented after 2 days of FMT, the same FMT course (15 capsules) will be repeated, up to 3 times. For patients in the antibiotic monotherapy group, an extension of the vancomycin treatment with the same doses will be given for 7 more days. Laboratory testing for the presence of C. difficile will not be required for the administration of repeated treatment, but will be annotated if performed. If symptoms will persist beyond day 18 of the study in both groups (8 days after the end of first treatment), we will allow treatment according to clinical judgement at the local study center. Patients will be free to decide if they want to stop their participation in the study at all times. Persistent symptoms beyond day 20 of the study will be considered as a clinical failure for the purposes of secondary outcome analysis. At any point, if there is a deterioration of the patient towards fulminant disease, clinical judgement will prevail as per protocol for fulminant cases.

During the study period and across study centers, we will encourage clinicians to use vancomycin as empiric treatment for pCDI. However, according to local clinical practice, patients may receive an antibiotic other than vancomycin (e.g. metronidazole). In both study groups, patients that were treated with another antibiotic agent in the first 24 hours, will be switched to vancomycin prior to day 3 of the study. The day of initiation of therapy will be considered from the first day of any antibiotic therapy that was administered. Randomization will be done within 72 hours from the initiation of any therapy for CDI.

In both groups, if a patient receives concurrent systemic antibiotics for other indications, the research team will contact the clinical team to understand if these antibiotics can be safely stopped 24 hours prior to randomization (day 3 from initiation of therapy). If systemic antibiotics cannot be stopped, then the patient will be excluded from the study.

In case of a CDI recurrence, the patient will be considered as reaching the primary outcome. We will permit treatment of CDI recurrences according to clinical judgement. We will provide Lyo-FMT for the treatment of recurrent CDI If available at the study center and required by the clinical team. In case of the development of fulminant disease, we will allow any therapy judged by the clinical team as appropriate. All cases with fulminant disease will be assessed by a surgical team for a timely fashioned colectomy if indicated. The development of fulminant disease from day 8 of the study onwards (3 days on FMT treatment) will be considered as clinical failure for the purposes of secondary outcome analysis.

The trial's primary efficacy outcome is the recurrence of CDI by week 8. Recurrence will be defined as the re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive C. difficile stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment. The primary outcome will be assessed by an observer blinded to study group assignment. ;

Related Conditions & MeSH terms

• Clostridioides Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Infections

• NCT number: NCT05709184
• Study type: Interventional
• Source: Rambam Health Care Campus
• Contact: Milena Pitashny, MD
• Phone: 972-4-7771108
• Email: m_pitashny@rmc.gov.il
• Status: Recruiting
• Phase: N/A
• Start date: November 15, 2023
• Completion date: March 2026