Efficacy and Safety of FMT for the Decolonization of MDROs in the Intestinal Tract

Efficacy and Safety of Fecal Microbiota Transplantation for the Decolonization of Multidrug-Resistant Organisms in the Intestinal Tract: An Unblinded Randomized Controlled Trial

The goal of this unblinded randomized controlled trial is to evaluate the efficacy and safety of fecal microbiota transplantation for the decolonization of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) or vancomycin-resistant Enterococci (VRE) in the intestinal tract. The study is planned to be conducted to test the superiority hypothesis that the decolonization success rate in the FMT group is higher compared to the non-FMT group. Outcome analysis will be conducted through intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis.

The main questions it aims to answer are:

• primary endpoint: Rate of Decolonization of Multidrug-Resistant Organisms (CP-CRE or VRE) at 1 Month After Fecal Microbiota Transplantation (FMT).
• secondary endpoint: Rates of Multidrug-Resistant Organism decolonization at 3 months, 6 months, and 1 year after FMT / Post-FMT Multidrug-Resistant Organism Recolonization Rate and Infection Rate.

Patients colonized with multidrug-resistant organisms in the gastrointestinal tract are divided into two groups through obtaining written consent from the patients and random allocation: the Fecal Microbiota Transplantation group (FMT group), which receives FMT, and the control group (non-FMT group), which is observed without FMT. The decolonization status of multidrug-resistant organisms will be monitored every 3-7 days after FMT until three consecutive negative results.

Study Overview

• Status: Recruiting
• Conditions: Carbapenem-Resistant Enterobacteriaceae; Vancomycin (Glycopeptide) Resistant Enterococcus (VRE)
• Intervention / Treatment: Procedure: fecal microbiota transplantation

Detailed Description

The study is planned to be conducted at Chuncheon Sacred Heart Hospital and Severance Hospital, using randomization with equal allocation to allocate patients into FMT (Fecal Microbiota Transplantation) and non-FMT groups. The study parameters are set with an alpha error of 0.05 and beta error of 0.2. Considering the findings from previous research, a delta value (effect size) was determined for sample size calculation. Based on this calculated sample size, for CP-CRE, 80 patients will be recruited in the FMT group compared to 68 patients in the non-FMT group. For VRE, 48 patients will be recruited in the FMT group compared to 44 patients in the non-FMT group.

Patients who have provided written consent for participation in the study will be required to maintain fasting starting from the evening before the procedure, after discontinuing broad-spectrum antibiotics for a minimum of 3-7 days. Subsequently, a bowel preparation will be carried out twice - the evening before and the morning of the procedure. Once the bowel preparation is complete, 1 hour before the procedure, patients will receive loperamide to reduce bowel movements and then proceed to the endoscopy suite.

Fecal microbiota transplantation (FMT) will be carried out with the acquired frozen donor stool, which will be thawed for 2 hours at room temperature following purchase and delivery from a stool bank, under the consent and supervision of the patient or guardian. Frozen stool from carefully screened donors who have passed the rigorous screening of both Stage 1 clinical assessment and Stage 2 laboratory tests (including evaluation for antibiotic resistance organisms) will be supplied from a stool bank of Microbiotix inc.

The FMT procedure will be conducted in collaboration with the research team in the Division of Gastroenterology. During the procedure, no tissue biopsy or excessive endoscope insertion will be performed. The FMT involves the simple infusion of thawed donor stool into the terminal ileum under colonoscopy, which takes approximately 5-10 minutes. The procedure carries minimal risk of bleeding, perforation, or aspiration. In most cases, it will be performed under sedation with a colonoscopy. If smooth insertion of the colonoscope or proper visualization of the colon is hindered, or if colonic preparation is not successful, Esophagogastroduodenoscopy (EGD) will be performed with sedation, and thawed donor stool will be infused into the third portion of the duodenum. This procedure also poses minimal risk of regurgitation or aspiration due to its anatomical and physiological characteristics. After the procedure, the lower extremities will be elevated by about 30 degrees to prevent the transplanted stool from exiting. A one-day fasting period will be maintained after the procedure to facilitate successful engraftment of the transplanted stool, followed by the gradual resumption of a regular diet. Following FMT, repeated rectal swab cultures will be conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-7 day intervals.

In cases where encapsulated fecal material is used for FMT, it will be ingested along with high-acid cranberry or orange juice. The capsules are specially designed to dissolve in low-acidic environments, allowing them to reach the terminal ileum for safe administration without the need for bowel preparation. On the first day, 15 capsules will be consumed, followed by another 15 capsules on the second day, for a total of 30 capsules. Subsequently, repeated rectal swab tests will be conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-day intervals.

According to patient random allocation, fecal samples and clinical metadata will be periodically collected (prior to FMT, 1 month, 3 months, 6 months, and 12 months after FMT) from both recipients and donors. These collected samples will undergo full-length 16S rRNA sequencing and shotgun metagenomic sequencing to comprehensively analyze the gut microbiome. Through this analysis, the aim is to elucidate the intestinal microorganisms associated with decolonization outcome and their mechanisms.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Seung Soon Lee, MD, PhD; Phone Number: +82-10-3379-9347; Email: hushh93@gmail.com
• Study Contact Backup: Name: Jun Yong Choi, MD, PhD; Phone Number: +82-10-4073-9253; Email: seran@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Jun Yong Choi, MD, PhD; Phone Number: 82-10-4073-9253; Email: seran@yuhs.ac
  • Gangwon-do
    • Chuncheon, Gangwon-do, Korea, Republic of, 24253
      • Recruiting
      • Chuncheon Sacred Heart Hospital
      • Contact: Seung Soon Lee, MD, PhD; Phone Number: +82-10-3379-9347; Email: hushh93@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individuals aged 20 and older.
2. Those with confirmed carbapenemase-producing Enterobacteriaceae (CPE) from a rectal swab culture within the past week (class A, B, or D CPE).
3. Those with confirmed vancomycin-resistant Enterococci (E. fecalis or E. faecium) from a rectal swab culture within the past week.
4. Individuals who have agreed to undergo Fecal Microbiota Transplantation (FMT) procedures and to provide pre- and post-procedure stool samples.
5. Individuals who have discontinued antibiotics for a period of 3 to 7 days prior to FMT procedure.

Exclusion Criteria:

1. Patients with ongoing or anticipated acute treatment, including antibiotic therapy.
2. Individuals with severe immunodeficiency.
3. Cases where there is a risk due to upper gastrointestinal endoscopy or colonoscopy.
4. Pregnant individuals, those who could become pregnant, and breastfeeding women.
5. Cases where participation in the study is determined by the researcher not to be beneficial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT group; fecal microbiota transplantation using frozen or capsulized stool	Procedure: fecal microbiota transplantation; Fecal microbiota transplantation will be conducted on patients using donor stool (frozen or capsulized stool) from a stool bank.
No Intervention: non-FMT group; Simple observation without intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Decolonization of Multidrug-Resistant Organisms at 1 Month After Fecal Microbiota Transplantation (FMT)	The decolonization rate at 1 month after FMT refers to the proportion of achieving three consecutive negative results within 1 month after the FMT procedure.	at 1 Month After Fecal Microbiota Transplantation (FMT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rates of Multidrug-Resistant Organism decolonization at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)	The decolonization rate at 1 month, 3 months, and 1 year after FMT refers to the proportion of achieving three consecutive negative results within 3 months, 6 months, and 12 months after the FMT procedure.	at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)
Post-FMT Multidrug-Resistant Organism Recolonization Rate and Infection Rate within 1 year after FMT	The rates of re-colonization of decolonized multidrug-resistant organisms (CP-CRE or VRE) and clinical infection rates of MDROs within 1 year after FMT procedure.	within 12 months after FMT

Collaborators and Investigators

• Sponsor: Chuncheon Sacred Heart Hospital
• Collaborators: Severance Hospital; National Institute of Health, Korea
• Investigators: Principal Investigator: Seung Soon Lee, MD, PhD, Chuncheon Sacred Heart Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 14, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Carbapenem-Resistant Enterobacteriaceae; Vancomycin-Resistant Enterococci
• Other Study ID Numbers: 2023-06-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No