Fecal Microbiota Transplantation for the Prevention of Infectious Complications After Liver Transplantation

Efficacy and Safety of Fecal Microbiota Transplantation for the Prevention of Early-onset Infectious Complications After Orthotopic Liver Transplantation

The increasing emergence and spread of MDRB represents a major public health problem, with higher mortality in patients experiencing infections. Cirrhotic patients listed for OLT and after OLT are at high risk of MDRB colonization or infection due to the large use of broad-spectrum antibiotics in the post-transplant setting. Therefore, effective decolonization strategies in this particular setting are urgently needed. The investigators hypothesize that heterologous FMT can reduce infections rates in the pre-and post- OLT setting by MDRB decolonization and restoration of a more physiological microbiome.

Study Overview

• Status: Recruiting
• Conditions: Fecal Microbiota Transplantation; Multi-drug Resistant Bacteria; Orthotopic Liver Transplantation
• Intervention / Treatment: Procedure: Fecal microbiota transplantation (FMT)

Detailed Description

The study is a double-blind, single-center, randomized controlled trial and will be offered consecutively to every adult patient on the liver transplant list.

Enrolled patients will be randomized (1:1) and assigned to either the heterologous or autologous fecal microbiota transplantation.

The intervention of the trial is heterologous fecal microbiota transplantation, which involves the administration of fecal material from a healthy donor into the intestine of the enrolled patient. Fecal samples will be collected every three months and before each microbiota transplant for evaluation of fecal microbiota composition. Gut permeability tests will be evaluated at enrollment and after the first fecal transplantation. Moreover, clinical and microbiota assessments will be performed after liver transplantation. All other planned assessments are part of the normal course of care.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giovanni Barbara, MD; Phone Number: +390512144103; Email: giovanni.barbara@unibo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Giovanni Barbara, MD; Phone Number: +390512144103; Email: giovanni.barbara@unibo.it
    • Principal Investigator: Giovanni Barbara, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult (age≥18 years) patients listed for OLT for various etiologies.
• Patient's consent to participate in the study

Exclusion Criteria:

• Previous total colectomy
• Pregnancy or breastfeeding
• Patients on oral or intravenous antimicrobial agents
• HIV positive and not well controlled on antiretroviral therapy, or CD4+ <200/ mm3
• Active SARS-CoV-2 infection
• Neutropenia <0.5X10^9/L
• Toxic megacolon
• Contraindications to colonoscopy
• Any conditions for which, according to the physician, FMT endangers the patient's health
• History of hypersensitivity to macrogol contained in bowel preparations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Heterologous FMT; Heterologous feces will be processed from routinely screened universal donors. Adult patients listed or being evaluated for enlistment for OLT for various etiologies are eligible for Fecal Microbiota Transplantation. Fecal material must be infused by enema or colonoscopy.	Procedure: Fecal microbiota transplantation (FMT); To assess if heterologous FMT is more effective than autologous FMT in reducing the rate of major infection episodes within 6-months after OLT.
Placebo Comparator: Homologous FMT; The control arm will undergo autologous FMT after enrollment. Autologous feces will be collected by each patient the day before each FMT in both study arms. This will guarantee adequate patients' stool collection in order to subsequently store the fecal samples for autologous FMT and ensure blinding.	Procedure: Fecal microbiota transplantation (FMT); To assess if heterologous FMT is more effective than autologous FMT in reducing the rate of major infection episodes within 6-months after OLT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess if heterologous FMT is more effective than autologous FMT in reducing the rate of major infection episodes within 6-months after OLT.	Incidence of clinically severe infections (sepsis, severe sepsis, septic shock)	At 6 months after OLT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events after FMT	To evaluate the safety profile of both heterologous and autologous FMT in patients enlisted for OLT and the relationship between fecal microbiota composition and the gastrointestinal permeability profile before and after FMT.	3 years

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Giovanni Barbara, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: FMT-OLT; Bando RF-2021-12373311 (Other Grant/Funding Number: Ministero della Salute)

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