Faecal Bacteriotherapy for Antibiotic-Associated Diarrhoea in Patients In Intensive Care - Randomised Controlled Trial
Phase: NA
Conditions: Diarrhea Caused by Drug, Clostridium Difficile Infections
Sponsor: Charles University, Czech Republic

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
 
 
 
Faecal Bacteriotherapy for Postantibiotic Diarrhoea in Critical-
ly Ill Patients – Randomised Controlled Trial  
 
Faecal Bacteriotherapy in Intensive Care 
ACRONYM: FEBATRIC 
 
Principal investigator:  
Dr Frantisek Duska, PhD, Dept. of Anaesthesia and Intensive Care Medicine, Charles 
University, 3rd Faculty of Medicine and FNKV University Hospital in Prague, Czech 
Republic 
 
Investigators:  
 
Dr Veronika Rehorova – Dept. of Anaesthesia and Intensive Care Medicine, Charles 
University, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr Anne LeRoy – Dept. of Anaesthesia and Intensive Care Medicine, Charles Universi-
ty, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr Ivana Cibulkova – Division of Gastroenterology, Dept of Medidine II, Charles Uni-
versity, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr Jan Gojda - Centre for Research on Diabetes, Metabolism and Nutrition, Dept of 
Medidine II, Charles University, 3rd Faculty of Medicine and FNKV University Hospital, 
Prague 
 
Marek Kuzma, PhD – Institute of Microbiology, Academy of Sciences of the Czech 
Republic 
 
Monika Cahova, PhD Department of Experimental Medicine, Institute for Clinical and 
Experimental Medicine, Prague 
 
Dr Petr Waldauf - Dept. of Anaesthesia and Intensive Care Medicine, Charles Univer-
sity, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr Michal Fric - Dept. of Anaesthesia and Intensive Care Medicine, Charles Universi-
ty, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
Dr Tomas Tencer - Dept. of Anaesthesia and Intensive Care Medicine, Charles Uni-
versity, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr Bob Bakalar - Dept. of Anaesthesia and Intensive Care Medicine and Burn Center, 
Charles University, 3rd Faculty of Medicine and FNKV University Hospital, Prague 
 
Dr. Robert Zajicek - Burn Center, Charles University, 3rd Faculty of Medicine and 
FNKV University Hospital, Prague 
 
Mrs Irena Kozakova, RN - Dept. of Anaesthesia and Intensive Care Medicine and Burn 
Center, Charles University, 3rd Faculty of Medicine and FNKV University Hospital, 
Prague 
 
Sponsor: Nadační fond Donatio intensivistam 
 
Sponsor Responsible Representative: Dr Frantisek Duska, PhD, Dept. of Anaesthesia 
and Intensive Care Medicine, Charles University, 3rd Faculty of Medicine and FNKV 
University Hospital in Prague, Czech Republic 
 
Study monitor: Mrs Irena Kozakova, RN - Dept. of Anaesthesia and Intensive Care 
Medicine and Burn Center, Charles University, 3rd Faculty of Medicine and FNKV Uni-
versity Hospital, Prague 
 
Trial registration number (clinicaltrials.gov): NCT EudraCT-2021-002290-25  
 
 
Abstract:  
Background: Postantibiotic diarrhoea in critically ill patients is common, often pro-
tracted  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 
curse of antibiotic therapy that is persistent for 24 hours even after interruption of 
enteral nutrition. Patients with septic shock or approaching death will be excluded.  
 
 
Treatment in the intervention group:  Faecal bacteriotherapy (FBT) delivered as en-
ema (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. infec-
tion).  
 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
Primary outcome: Percentage of patients with treatment failure at day 7 after ran-
domisation, which is defined as treatment either not being delivered or effective.  
Secondary and exploratory outcomes: Influence of the intervention on colonic mi-
crobiom and metabolom, small bowel and colonic permeability, bacterial transloca-
tion and systemic inflammation.  
 
Background:  
Over 80% of critically ill patients receive antibiotic treatment over their ICU stay and 
it is well documented that it leads in a reduction of the diversity of colonic bacterial 
flora. In turn, this leads to overgrowth of pathogenic species incl. Clostridium difficile 
(C.dif.) and multi-drug resistant Enterobacteriaceae and Enterococci. Restoration of 
physiological bacterial flora is prolonged and a significant proportion of patients suf-
fer from postantibiotic diarrhoea. In particular, postantibiotic diarhea in the critically 
ill that is associated with C. dif. infection may lead to prolonged ICU stay or compli-
cations such as toxic megacolon, sepsis and death. Even non-clostridial postantibiotic 
diarhoea represent a significant burden to ICU patients and staff, impairing patients 
dignity and comfort and often increasing their length of stay. Current treatment op-
tions are limited as neither prebiotic nor probiotic were found to be consistently ef-
ficient in the critically ill and have been found risky in some settings, e.g. pancreati-
tis. Changes of colonic microbiome are well documented in the critically ill and 
length and mechanisms of restoration of colonic microbiome are yet unknown.  It is 
also unknown to what extent changes in colonic flora contribute to nosocomial in-
fections by MDR Gram negatives in the critically ill.  
In the light of this, restoring physiological bacterial flora in the colon by faecal bacte-
riotherapy (FBT) could potentially be beneficial. FBT has been shown to be safe and 
effective not only in the prophylaxis of recurrence after the antibiotic treatment, but 
also as the first-line treatment in the population of non-critically ill patients with C. 
dif. infections .  
 
The study will be performed in accordance with the protocol, The Declaration of Hel-
sinki and principles of Good Clinical Practice: Consolidated Guidelines. The protocol 
is consistent with any applicable local regulations. 
 
Hypothesis and aims:  
We hypothesise that FBT will be feasible as first-line treatment of postantibiotic diar-
rhoea in the critically ill, incl. those with uncomplicated C. dif. infection.  
 
 
Primary end-point:  
• Percentage of patients with treatment failure at day 7 after randomisation. 
Treatment failure is defined as either failure to administer allocated treatment 
for any reason or the presence of diarrhoea on day 7 after randomisation (as as-
sessed by personnel blinded to treatment allocation). 
   

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
 
 
 
Secondary end-points are:  
• Composite number of adverse events such as new-onset sepsis, toxic mega-
colon, positive post FBT blood culture, or other SAE assessed by the physi-
cian-in-charge as possibly related to FBT. 
• SOFA score at days 4 and 7.  
• Percentage of patients that are recurrence-free at time of hospital discharge 
or day 28, whichever occur earlier. 
• Subgroup analysis will be performed for patients who are C. dif. positive vs. 
negative and those who will receive antibiotics for a new extraabdominal in-
fection vs. those who do not.  
 
Exploratory outcomes: 
• Diversity, density and composition of faecal microbiome by quantitative se-
quence-based mapping  
• Changes in bowel metabolom incl. bile acid spectrum as assessed by NMR 
and GS/MS 
• Bowel barrier integrity and inflammation assessed by plasma markers (citrul-
line, endotoxin, D-lactate, IL-6, IL-8, IL-12, TNF-a, LL-37 cathelidicine), faecal 
markers (calprotectine) 
• Donor’s diversity and viability of faecal microbiome by quantitative 
sekvence-based mapping and cultivation  
 
 
Method: 
Design: prospective, randomised, controlled, parallel group, open-label, assessor 
blinded feasibility trial.  
 
Study subjects:  
• Inclusion Criteria: All of the following: Informed consent (see below), Age > 
18 yrs., In-patient in ICU or HDU (incl. burn unit) and expected to stay for >7 
days, Diarrhoea 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. Pa-
tients with a history of severe anaphylactic food allergy, any other reason 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
which – as per judgement of the treating clinician – makes faecal transplanta-
tion 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).  
 
 
Selection of donors and preparation of stool extract for FBT: 
The selection and assessment of donors will be performed after obtaining a written 
informed consent from them (see Appendix 1) and in accordance with Guidelines for 
faecal bacteriotherapy (version May 2018, issued by Czech Society of Infectious Dis-
eases, https://www.infekce.cz/DPFMT18.htm). The donors will be recruited mainly 
but not exclusively from volunteers donating their stool samples for another trial 
(Gojda et. al., NCT No), looking at the difference of intestinal microbioma between 
vegans and omnivores. We will only recruit donors into this study from the omniv-
orous cohort. After filling a pre-specified questionnaire (see Appendix 2), detailed 
history and physical examination will be performed.  
Afterwards, the standardized donor work-up will include:  
- 
Blood: full blood count incl. WBC differential, Sedimentation Rate, CRP, liver 
function tests (ALT, AST, ALP, GMT, bilirubin), creatinine, albumin and level of 
glucose , HIV (p24 and anti HIV-1 and 2), syphilis serology (RRR or TPPA) and 
hepatitis panel (HBsAg, anti-HBc IgM and IgG, HBeAg, anti-HBc total, anti-HCV, 
anti-HAV, anti-HEV) 
- 
Stool examination: C.dif. (GDH and toxin A and B), cultivation to detect Shigella, 
Campylobacter, Listeria,Pseudomonas, Enteropathogenic E.coli 
(EPEC,EAEC,ETEC,EIEC), Yersinia and Salmonella sp.,Vibrio cholerae, MDRO 
(VRE, ESBL,CRE) , standard microscopy  parasitological exam (Giardinia lamblia, 
Cryptosporidium parvum, Isospora, Microsporidia, Entamoeba histolytica) and 
from virological exam will be performed PCR CMV, Rotavirus, Norovirus. Fecal 
occult blood test. 
- 
Nasopharyngeal swab – PCR to rule out COVID-19 infection 
– Culture based assay MRS 
 
The aim of the basic blood test is to confirm the patient's good clinical condition. The 
aim of other tests is to prevent the transmission of latent infection from the donor 
to the recipient. This complete examination of the donor is repeated after 2 months. 
If the following examination is also found to be physiological (ie without signs of the 
donor's infectious disease), the stool donated by the donor during these 2 quaran-
tine months (frozen in the stool bank) will be considered non-infectious and can be 
used for the FBT method. Despite this quarantine measure, the donor is obliged to 
fill in a questionnaire focusing on the risks of infectious diseases during each delivery 
of stool. In case of a new occurrence of infectious manifestations (especially diar-
rhea) travelled abroad or taken antibiotics the stool donor is obliged to inform about 
this attending physician. 
 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
Stool collection from the donor: 
For better timing of defecation, the donor will use glycerine suppositoria (Supposito-
ria Glycerini 2,06g). The stool will be captured via Fe-Col Faecal Collection paper 
(Eastoport) and  transported in a sterile container (container 2000ml,  Sarsted) to the 
place of processing as quicly as possible, but no later than 4 hours from defecation.  
 
Preparation of stool extract: 
The stool will be processed as soon as possible, but no later than 6 hours after defe-
cation. The stool is weighted and mixed (hand blender, Mulinex) with normal saline 
1:3, mixed thoroughly and filtered through 2 layers of gauze to remove solid parts.  
Afterwards, glycerine will be added to final concentration 10% and the final micture 
is divided into 50 ml sealed containers, labelled and immediately stored at -80 C for 
up to 12 months.  
In order to minimise the homogeneity of the transplantate, 2 hours before trans-
plantation, 7 aliquotes from 7 donors will be thawed at 37C water bath and drawn 
into the irrigation syringes/bags. Immediately afterwards, the extracts must be 
drawn into a sterile syringe and the resulting transplant administered to the recipi-
ent. Re-freezing of thawed or partially thawed extract is not permitted. The use of 
frozen stool does not reduce the effectiveness of faecal bacteriotherapy if the used 
graft is stored at -80 ° C for a maximum of 12 months. 
 
   
Sample study size:  
We plan to randomise 36 patients in 1:1 ratio: This is a pilot trial, with primary out-
come being feasibility and safety of faecal bacterial transplantation in the population 
of critically ill adults with C. dif. positivity and diarrhoea. However, with 36 random-
ised patients, the study will have sufficient power to determine non-inferiority 
against standard-of-care based on data available in FBT in patients with C. dif.  In two 
trials in non-critically ill patients, the success of FBT was 69% (22 out of 32) or 56% (5 
out of 9) as compared to 45% cured by oral metronidazole. Assuming that clinically 
significant difference between the two methods is 20% and the intervention will be 
as effective in ICU patients as it was in the non-critically ill group (curing 27 out of 41, 
ie. 66%), if there is a true difference in favour of the experimental treatment of 21%, 
then 36 patients are required to be 80% sure that the upper limit of a one-sided 95% 
confidence interval (or equivalently a 90% two-sided confidence interval) will ex-
clude a difference in favour of the standard group of more than 20%. The expected 
duration of participation in the study is 6 months. 
 
 
Informed consent procedure:  
All patients with capacity will be asked to provide a prospective written informed 
consent (See Appendix 3). For patients without capacity, a deferred consent proce-
dure will take a place. In this case, an independent clinician will review and sign that 
the patient is lacking capacity and he/she fulfils all criteria to be enrolled to the 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
study. The patient’s next of kin will be informed about the study as soon as practical 
with the aid of information leaflet (Appendix 3). The patient will be asked to provide 
and sign informed consent as soon as he/she regains the capacity to do so. In case of 
consent refusal, patient’s data will not be used in per-protocol analysis.  
 
 
 
 
 
 
 
 
ICF, Baseline  
stool, stop EN 
If ongoing diarhea, X-ray 
RANDOMISE 
STANDARD 
OF CARE 
Perform FBT 
(if C. dif. add lavage + repeat 
FBT after 24 hours) 
D7 
Assess primary outcome 
Stool and plasma samples, TSA 
test 
Next day 
Treat diarrhoea per protocol 
(if C. dif. - vancomycine) 
250mg  mg x4 /day) 
Monitor diarhea + adverse 
events daily, stool + serum 
sample at D4 
Day  1 
Monitor diarhea + clinical 
course daily, stool + serum 
sample at D4 
Day 2-6 
INTERVEN-
TION 
GROUP 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
 
Procedures at baseline:  
 
Day 0 
In patients with diarhea, after confirmation of negative pregnancy test in fertile women in-
formed consent will be subscribed. The drug chart will be reviewed and all medication that 
can be contributing to diarhea will be stopped if it is considered safe to do so. Abdominal X 
ray will be performed to rule out pneumoperitoneum or megacolon.  After obtaining base-
line stool sample (sent for study analyses but also for GDH, C. dif. toxins A and B and faecal 
calprotectin), blood sample will be tested for standard tests ( biochemistry, blood count, 
etc.). Stool and plasma samples will be frozen at -80 C for later analysis. 
Randomisation will be performed by sealed envelope in the evening of day No.0. En-
teral nutrition will be stopped at 18:00 at the latest.  
 
Day 1 
The patient will be physically examined in the morning, including the determination 
of the degree of SOFA score (a set of laboratory results and examinations estimating 
organ function).  Stool and plasma samples will be frozen at -80 C for later analysis. 
The frequency, amount and structure of the patient's stools will be recorded.  Pa-
tients will be treated for their primary disease throughout the study according to es-
tablished standard procedures.  
In both groups adequate hydratation will be taken care of by replacing the fluids lost 
by diarrhea with infusion. Throughout the treatment, we monitor the patient’s vital 
functions (body temperature, heart rate, blood pressure, blood oxygen saturation) 
 
• Control group:  
-  we will wait for spontaneus retreat of diarrhea, which is a standard of care.  
- in the subset of patients with C. dif. positivity, the patients receive 250 mg of 
vancomycine every 6 hour (with rescue option of conversion to  i.v. tigecy-
cline).    
 
• Intervention group :  
- 
if considered safe, the patient receive Loperamide 2 mg p.o. 2  hours be-
fore FBT.  
- 
FBT procedure - 350 ml of thawed donor stool (stool suspension) will be 
delivered by retention enema in the patients colon. The patient will be 
positioned in left semilateral Trendelenburg's position for 15 minutes and 
then in right semilateral Trendelenburg’s position for another 15 minutes. 
Faecal management system (e.g. FlexiSeal©) will be inserted and 
clamped for 2hours after FBT 
- 
in all patients receiving FBT will be recorded body temperature, heart 
rate, oxygen saturation and blood pressure. 3hours after FBT blood cul-
ture will be taken.  

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
- 
in the subset of patients with C. dif. positivity, 1 L normal saline enema 
will be performed at the time of CDI  diagnosis and FBT will be repeated 
once more. No antibiotics will be administered (with rescue option of 
administration of   i.v. tigecycline). 
 
FBT stool suspension will be stored in specific −80°C freezer with connected alarm 
notification to guarantee continuous registration of the storage. Information on the 
FBT suspension labels includes donor code, suspension number, production and ex-
piration date, volume, and storage temperature instruction. From each donor one of 
the sample will be store in freezer for the duration of the ongoing study.  
The resulting faecal bacteriotherapy (FBT) preparation is defined as a mixture of 7 al-
iquots of processed stool intermediates from 7 donors. 
The resulting graft will be drawn into four sterile 100 ml syringes and transferred to 
the ward where the recipient is hospitalized. Re-freezing of thawed or partially 
thawed extract is not permitted. 
 
 
Day 2, 3 
Physical examination, SOFA score, evaluation of laboratory blood results (WBC, CRP, 
lactate, etc.) will be recorded as well as volume or frequency and consistency (Bristol 
scale) of stool. Concomitant medication and adverse events will be recorded.  
Day 4 
As above day 2,3 plus obtain stool + plasma samples, freeze -80 C 
Day 5, 6 
see Day 2, 3 
Day 7 
Primary outcome assessment (see below) followed by collection of plasma and fae-
cal samples.   
 
Assessment of primary outcome:  
An independent data analyst will retrospectively review the de-identified  printouts 
of nursing notes from the two 12 hour shift day + night ending in the morning of day 
7 and record the presence or absence of diarrhoea (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-
serted). 
In case the patient is not on ICU, but remains at hospital, the research nurse will 
bring a special record form on day 6 and instruct both the patient and nursing staff 
to record during the next 24 hours the volume or frequency and consistency of stool 
using visual Bristol Scale and also to provide a sample of stool. In case the patient 
has been discharged, he/she will be contacted the day before over the phone by a 
research nurse and the next day the patient will be asked to bring the formulary and 
a stool sample to hospital of will be visited by a research staff at home.     
Afterwards, as long as the patient remains on ICU, adverse events, antibiotic treat-
ment, and stool volume/frequency are monitored daily.  

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
In patients with faecal management device in place, follow up visits (identical to Day 
4) are performed in 7 days interval up to day 28, and/or ICU discharge or FMD re-
moval, whichever occurs earlier.  
In patients who remain in ICU, but have had FMD removed, have the same follow up 
procedures, with the exception of stool sampling. Stool is collected and stored as 
close as practical to the day of the visit after the patient has had spontaneously def-
ecated. 
In patients who are not on ICU, but remain at hospital, will be visited by a research 
nurse at day 7, 14, 21 and 28 as long as they remain hospitalised. The visit will in-
clude monitoring of adverse event, notice on patient general status, the pres-
ence/absence of diarrhoea, antibiotic medication. Blood will be collected and frozen. 
Six month follow up is performed at follow up clinics and it includes history (incl. re-
cent history of diarrhoea), physical exam and blood sampling. Patients willing to do 
so are requested to bring in a stool sample.  Patients unwilling to show up will be in-
terviewed over the phone. 
 
 
 D0  
D1 
D2 
D3 
D4 
D 5-6 
D7 D14, 21, 
28or D/C 
6month 
follow up 
ICF 
x 
 
 
 
 
 
 
 
 
Review drug chart 
x 
 
 
 
 
 
 
 
 
Serum 
sample 
+ 
freeze 
x 
x 
 
 
x 
 
x 
x 
x 
Stool sample + 
freeze 
x 
 
 
 
x 
 
x 
(x) 
x 
Adverse events, 
Phys.exam, SOFA 
x 
x 
x 
x 
x 
x 
x 
x 
 
Blood culture 
 
x x 
 
 
 
 
 
 
 
Primary 
outcome 
assessment 
 
 
 
 
 
 
x 
 
 
in 
intervention 
group -FBT 
 
x 
 
 
 
 
 
 
 
 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
 
 
Table: Gantt diagram of study procedures. See text for details.  
 
Monitoring of safety:  
Although it is potentially beneficial and has been safely performed in ICU patients, there are 
only limited data about FBT safety in patients with potentially disrupted intestinal barrier. In 
turn, following measures have been taken to maximise safety of the current study for pa-
tients:   
 
• Treating clinician will not be blinded to treatment allocation and they will be encour-
aged to speak up should any safety concerns arise.  
• Before and 3 hours after FMT, vital signs, blood cultures, endotoxin and early cyto-
kine levels will be measures to specifically look at potential bacterial translocation.   
• All patients’ vital functions will be continually monitored as per local standards. Fre-
quency, volume and character (as per Bristol scale) of stools will be recorded in 12 
hour intervals. 
• Onset of sepsis or elevation lactate > 2mM or the presence of pyrexia >38 C with 
>30% rise of inflammatory markers without clear alternative reason (e.g. HAP) will 
trigger, in both groups, the addition of intravenous tigecycline or intravenous van-
comycine, if C. dif positivity is known or suspected.  
• I.v. antibiotics efficient against C. dif. can be added in both groups if a treating clini-
cian considers this appropriate. Reason for doing so will be recorded.  
• Should a SUSAR appear, it will be reported as per local legislature and within 48 
hours reviewed by the team of investigators, together with independent safety advi-
sors (prof. Jiri Benes. Dept. of Infectious Diseases, Na Bulovce Hospital, Prague and 
Dr.Martin Herold, REB Chair FNKV Univ. Hospital), a representative of nursing staff 
independent on the study.  Two SUSARs in the intervention group would automati-
cally lead to termination of the trial for safety reasons.  

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
• In addition, the same team will meet ad hoc whenever safety concerns arise. The 
team will review data collected from first 8 subjects who have been randomised and 
focus on the analysis of adverse events. In particular, the team will review the dy-
namics of body temperature, heart rate, blood pressure, lactate and blood cultures 
before and after FMT. The decision will be taken to continue or terminate the study.   
 
Statistical plan:  
Safety parameters will be reported on intention-to-treat basis. Primary outcome will be 
compared by as unadjusted hazard ratio of not being cured (with 95% interval) in a per pro-
tocol analysis.  The subset of patients with C. dif positivity will be analysed separately.  
 
Direct access to source data/documents:  
Whole FBT procedure must be properly recorded in accordance with the rules on medical 
records and the documentation must be store for 10 years. The patient documentation shall 
include the performance indication, performance record, informed consent to FBT and in-
formation obtained during subsequent visits. The documentation must be kept to allow for 
an additional assessment of possible early and late side effects of the method. Furthermore, 
it will be recorded from what 7 donors the extract was used for each individual patient. 
Donor documentation includes the results of clinical and laboratory testing, a completed 
and signed questionnaire confirming the absence of exclusion criteria and informed consent 
to the use faeces for medical purposes.  For each frozen faecal extract, the date of freezing 
and, where appropriate, the place of preservation must be indicated in addition to the do-
nor identification. 
The examiner and the medical facility will allow for clinical trial monitoring, audits, oversight 
of the ethics committee, inspection authorities inspection and access to source documents. 
 
Quality control and quality assurance:  
To ensure compliance with Good Clinical Practices and all applicable regulatory require-
ment. 

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
 
Ethics:  
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favourable opinion in writing by in the Ethics Committee (EC) as appro-
priate. The Investigator is also responsible for informing the EC of any amendment to the 
protocol in accordance with local requirements. The investigator is also responsible for 
providing the EC with reports of any serious side effect of FBT therapy. 
The study will be performed in accordance with the protocol, ethical principles that that 
have their origin in the Declaration of Helsinki WMA, and are consistent with Good Clinical 
Practice: Consolidated Guidelines and any applicable local regulation. 
The Investigator(s) will ensure that subject (or the legal representative) is given full and ad-
equate oral written information about the nature, purpose, possible risk and benefit of the 
study. Subject must also be notified that they are free to discontinue from the study any 
time. The subject (or the legal representative) should be given the opportunity to ask ques-
tions and allowed time to consider the information provided. 
Voluntary written informed consent must be obtained before any study-related procedures 
are performed and the Investigator(s) must maintain the original, signed Informed Consent 
Form. 
 
Data handling and recordkeeping:  
The team of investigators, together with independent safety advisors (prof. Jiri Benes. Dept. 
of Infectious Diseases, Na Bulovce Hospital, Prague and Dr. Martin Herold, REB Chair FNKV 
Univ Hospital) and representative of nursing staff independent on the study, are allowed to 
inspect subject charts, study source documents, drug accountability records and other rec-
ords relative to study conduct. The Investigator must maintain all documentation to the 
study for a period of 5years after the end of last study subject. 
 
Publication Policy:  

Klinika anesteziologie a resuscitace  
3. lékařská fakulta Univerzity Karlovy  
a Fakultní nemocnice Královské Vinohrady Šro-
bárova 50, 10034, Praha 
Faecal Bacteriotherapy in Intensive Care 
Acronym: FEBATIC 
Unique Protocol ID: 2021-002290-25 
22.9.2021 Protocol version 9.2 
 
We follow the authorship criteria established by the international Committee of medical 
Journal editors.  
Minimum criteria for authorship credit based on:  Substantial contributions to conception 
and design, acquisition of data or analysis and interpretation of data. Drafting the article or 
revising it critically for important intellectual content and final approval of version to be 
published. To be considered, all potential authors must fulfil all the minimum criteria for 
authorship credit. 
 
 
1. 
Dorsaz, S. et al. Changes in Microbiota Profiles After Prolonged Frozen Storage of 
Stool Suspensions. Front. Cell. Infect. Microbiol. 10, 1–8 (2020).