Faecal Bacteriotherapy for Postantibiotic Diarrhoea in Critically Ill Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Diarrhea Caused by Drug, Clostridium Difficile Infections

Intervention / Treatment
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* Other: Faecal bacteriotherapy (FBT)
* Other: standard-of-care protocolised treatment of postantibiotic diarhea


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, single center, parallel group randomised controlled trial.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiota, critically ill, fecal microbial transplantation