Faecal Bacteriotherapy for Postantibiotic Diarrhoea in Critically Ill Patients (FEBATRICE)

Faecal Bacteriotherapy for Antibiotic-Associated Diarrhoea in Patients In Intensive Care - Randomised Controlled Trial

Rationale: Postantibiotic diarrhoea in critically ill patients is common, often prolonged and currently there is no effective treatment of it.

Aim: To test safety and feasibility of faecal microbial transplantation in critically ill patients with postantibiotic diarhoea.

Design: Prospective, single center, parallel group randomised controlled trial. Subjects: ICU patients (both general and burn ICU) who developed diarhea after a course of antibiotic therapy that is persistent for 24 hours and is not due to other causes. Patients with septic shock or approaching death will be excluded.

Treatment in the intervention group: Faecal bacteriotherapy (FBT) delivered as enema (and repeated once in the subgroup of patients with C. dif. infection) of 350 ml of standardised mixed transplantate prepared from faeces of 7 healthy donors.

Control group: Standard-of-care protocolised treatment of postantibiotic diarhea (which includes vancomycine 250 mg p.o. 6 hourly in the subgroup with C. dif. infection).

Primary outcome: Percentage of patients with treatment failure at day 7 after randomisation, which is defined as treatment either not being delivered or not being effective.

Secondary and exploratory outcomes: Influence of the intervention on colonic microbiome and metabolome, small bowel and colonic permeability, bacterial translocation and systemic inflammation response to procedure.

Study Overview

• Status: Recruiting
• Conditions: Diarrhea Caused by Drug; Clostridium Difficile Infections
• Intervention / Treatment: Other: Faecal bacteriotherapy (FBT); Other: standard-of-care protocolised treatment of postantibiotic diarhea

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 10034
    • Recruiting
    • Kralovske Vinohrady University Hospital
    • Contact: Frantisek Duska; Phone Number: +420267162451; Email: frantisek.duska@fnkv.cz
  • Česká Republika
    • Praha, Česká Republika, Czechia, 10034
      • Recruiting
      • František Duška
      • Contact: František Duška; Phone Number: 608405541; Email: fduska@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signing of informed consent (see below)
• age > 18 yrs.
• in-patient in ICU or HDU (incl. burn unit) and expected to stay for >7 days
• diarrhea following antibiotic treatment defined as 3 or more stools per day or Bristol type 7 stool in the volume >300 ml/day if stool derivative device is in place, persisting for 24 hours despite enteral feeding formula has been stopped.

Exclusion Criteria:

• death appears imminent or ceilings of care put in place
• presence of new-onset sepsis defined as per 2016 definition
• lactate >2.0 mM, colon diameter > 9 cm on plain AXR
• the necessity of ongoing antibiotic treatment for another reasons
• unable to tolerate enema for any reason (e.g. surgery of the GI tract in the past year)
• pregnant and lactating woman
• patients with a history of severe anaphylactic food allergy, any other reason which - as per judgement of the treating clinician - makes faecal transplantation unsafe or not feasible (Note: All screening failures based on this criterion will be reported separately, inc. the reason why it was considered unsafe or not feasible to proceed).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention group; ICU patients who developed diarhea after a course of antibiotic therapy treated with Faecal bacteriotherapy (FBT) delivered as enema	Other: Faecal bacteriotherapy (FBT); Enema of 350 ml of standardised mixed transplantate prepared from faeces of 7 healthy donors.
ACTIVE_COMPARATOR: Control group; ICU patients who developed diarhea after a course of antibiotic therapy treated standard-of-care protocolised treatment of postantibiotic diarhea	Other: standard-of-care protocolised treatment of postantibiotic diarhea; standard-of-care protocolised treatment of postantibiotic diarhea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	Difference of proportion of patients between intervention and control groups in whom the treatment failed. Failure is defined as treatment has either not been delivered or has not been effective to cure diarrhoea as per WHO definition	7 days after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of therapeutic efficacy	Difference of proportion of patients between intervention and control groups who are diarhoea-free (WHO definition)	7 days after randomisation
Systemic inflammation	Difference between intervention and control group in area under C-reactive protein plasma concentration curve	7 days after randomisation
Organ failures	Difference between intervention and control group in SOFA score curve	7 days after randomisation
Postprocedural bacteriaemia	Difference between intervention and control group in the percentage of positive blood cultures	3 hours after intervention
Mortality	Difference between intervention and control group in the absolute risk of death (intention-to-treat analysis)	28 day or hospital discharge, whichever occurs earlier

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Collaborators: Faculty Hospital Kralovske Vinohrady; Donatio Intensivistam Endowment Fund

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 9, 2023
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): July 1, 2025

Study Registration Dates

• First Submitted: April 3, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (ACTUAL): June 24, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: critically ill; gut microbiota; fecal microbial transplantation
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections
• Other Study ID Numbers: 2021-002290-25

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