Clinical trial NCT06001333: Efficacy and Safety of FMT for the Decolonization of MDROs in the Intestinal Tract
Official title: Efficacy and Safety of Fecal Microbiota Transplantation for the Decolonization of Multidrug-Resistant Organisms in the Intestinal Tract: An Unblinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Carbapenem-Resistant Enterobacteriaceae
Vancomycin (Glycopeptide) Resistant Enterococcus (VRE)
Keywords: Carbapenem-Resistant Enterobacteriaceae
Vancomycin-Resistant Enterococci
Fecal Microbiota Transplantation
Gastrointestinal Microbiome
Lead sponsor: Chuncheon Sacred Heart Hospital
Sponsor class: OTHER
Collaborators: name: Severance Hospital
name: National Institute of Health, Korea
First posted: 2023-08-21
Enrollment: 240
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Decolonization of Multidrug-Resistant Organisms at 1 Month After Fecal Microbiota Transplantation (FMT)
timeFrame: at 1 Month After Fecal Microbiota Transplantation (FMT)
Secondary outcomes:
measure: rates of Multidrug-Resistant Organism decolonization at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)
timeFrame: at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)
measure: Post-FMT Multidrug-Resistant Organism Recolonization Rate and Infection Rate within 1 year after FMT
timeFrame: within 12 months after FMT
Other outcomes:
Locations:
city: Chuncheon
country: Korea, Republic of
facility: Chuncheon Sacred Heart Hospital
state: Gangwon-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Chuncheon Sacred Heart Hospital
name: Seung Soon Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: