RecruitingNot ApplicableNCT05709184

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

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

Sponsor

Rambam Health Care Campus

Enrollment

196 participants

Start Date

Nov 15, 2023

Study Type

INTERVENTIONAL

Conditions

Clostridioides Difficile Infection

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

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 Criteria19

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.

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Interventions

COMBINATION_PRODUCTLyophilized fecal microbiome transfer

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.

DRUGVancomycin

Ten days of oral vancomycin 125 mg four times daily