Fecal Microbiota Transplantation, Multi-drug Resistant Bacteria, Orthotopic Liver Transplantation
Conditions
Brief summary
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.
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.
Interventions
PROCEDUREFecal 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.
Sponsors
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
All adult patients listed or being evaluated for enlistment for OLT for various etiologies are eligible for inclusion in the present study. Study enrollment will start after the favorable opinion of the Ethics Committee and the authorization by the General Manager of IRCCS AOUBO, in May 2023, indicatively, and will last 24 months.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess if heterologous FMT is more effective than autologous FMT in reducing the rate of major infection episodes within 6-months after OLT. | At 6 months after OLT | Incidence of clinically severe infections (sepsis, severe sepsis, septic shock) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events after FMT | 3 years | 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. |
Countries
Italy
Contacts
Primary ContactGiovanni Barbara, MD
Outcome results
None listed