A clinical trial to test whether treating patients with liver cirrhosis with capsules containing healthy stool bacteria or a dummy capsule (placebo) will reduce the time it takes to develop an infection resulting in hospital admission

ISRCTN	ISRCTN17863382
DOI	https://doi.org/10.1186/ISRCTN17863382
ClinicalTrials.gov (NCT)	NCT06461208
Clinical Trials Information System (CTIS)	2022-000300-35
Integrated Research Application System (IRAS)	1004822
Protocol serial number	Nil known
Sponsor	King's College Hospital NHS Foundation Trust
Funder	Efficacy and Mechanism Evaluation Programme

Submission date: 14/03/2022
Registration date: 25/03/2022
Last edited: 13/02/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Our body contains trillions of bacteria. Many of these live in our bowels which keeps us healthy and helps our immune system to fight against infections. However, an increased number of ‘unfriendly’ bacteria are found in the bowel of patients with liver cirrhosis (permanent liver damage), which makes them highly susceptible to infections. Antibiotics are becoming less effective as they are used so frequently, and the bowel can become infected with ‘super-bugs’.

Replacing the unfriendly bowel bacteria in patients with cirrhosis with healthy bacteria donated from healthy volunteers (faecal microbiota transplantation) could be highly beneficial and reduce antibiotic usage. Findings from the initial FMT trial (the PROFIT trial) showed that FMT administered during endoscopy was safe with no serious side effects. However, patients said that they would prefer to take tablets rather than have an endoscopy.
The researchers have therefore made an FMT capsule from freeze-dried stool and this study will test whether treating patients with these FMT capsules reduces their likelihood of getting an infection.

Who can participate?
Patients aged 18 years and above who have been diagnosed with alcohol-related cirrhosis (ALD) or metabolic dysfunction-associated steatotic liver disease (MASLD) (previously referred to as non-fatty alcoholic fatty liver disease) or MetALD cirrhosis (a combination of the two types of liver disease) at any time point.
What does the study involve?
Participants will be selected at random to take FMT capsules or 'dummy’ capsules that contain no FMT (placebo) and both the study team and the participants will not know which treatment they are taking. The participants will need to take five capsules every 3 months for a total of 21 months or until they develop their first infection leading to hospital admission and will be followed up for a maximum of 2 years. This study will also examine whether FMT reduces the side effects of cirrhosis and has beneficial effects on the liver and immune system. The researchers will look at whether FMT reduces hospital admissions, the incidence of ‘super-bug’ infections and death. Laboratory studies will look at whether FMT treatment will help the immune system fight infection.

What are the possible benefits and risks of participating?
Patients will be taking part in a new and innovative trial to assess the beneficial effects of FMT capsules in patients with cirrhosis. There are no curative treatments available to patients with cirrhosis, aside from liver transplantation. Unfortunately, due to the scarcity of donor organs, even those listed for transplant can wait months or even years for a new liver. Others are too unwell or frail or deemed ineligible to be listed for a liver transplant.
The researchers will also gather information during the trial on how the FMT works in patients with cirrhosis including the impact on the make-up and function of the gut microbiome. They will examine whether FMT can reduce the likelihood of developing an infection and being admitted to the hospital.
There are no risks involved in taking part with regard to the samples being obtained, and the amount of blood taken will not be harmful to the patient. The placebo treatment is not harmful but is not expected to have any benefit as it contains no active drug or treatment. All patients, regardless of whether they receive placebo or FMT have the same rigorous follow-up and support from the trials team. They will be closely monitored after the treatment is given and will be seen at regular intervals afterwards to see if they have experienced any side effects. The researchers do not anticipate any serious problems to occur after the FMT or placebo treatment, but the participants will be given contact numbers should they run into any problems outside of the trial visits.
Where is the study run from?
King’s College London and King's College Hospital NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
November 2021 to June 2028

Who is funding the study?
National Institute for Health Research Efficacy and Mechanism Evaluation (NIHR) (UK)

Who is the main contact?
1. Prof. Debbie Shawcross (Chief Investigator), debbie.shawcross@kcl.ac.uk
2. Ms Sue Cheung, promise@kcl.ac.uk

Contact information

Prof Debbie Shawcross
Principal investigator

Institute of Liver Studies
King’s College Hospital and King’s College London
Denmark Hill
London
SE5 9RS
United Kingdom

Phone	+44 (0)203 299 3713
Email	debbie.shawcross@kcl.ac.uk

Ms Sue Cheung
Public

Research Management and Innovation Directorate
Institute of Psychiatry
16 De Crespigny Park
Denmark Hill
King’s College London
London
SE5 8AF
United Kingdom

Phone	+44 (0)20 7848 0532
Email	promise@kcl.ac.uk

Study information

Primary study design	Interventional
Study design	Multicentre randomized double-blind parallel-group placebo-controlled multi-centre trial
Secondary study design	Randomised parallel trial
Scientific title	A PROspective randomised double-blind parallel-group placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve the primary outcomE (first hospitalisation due to infection) in patients with cirrhosis over 24 months (PROMISE)
Study acronym	PROMISE
Study objectives	Current study objectives as of 13/02/2026: The researchers will perform a clinical trial to test whether treating patients with alcohol-related (ALD), metabolic dysfunction-associated Steatotic liver disease (MASLD) and MetALD cirrhosis with faecal microbiota transplantation (FMT) capsules vs placebo capsules will reduce the likelihood of them getting an infection or decompensating episode by measuring the time it takes to develop an infection or decompensating episode resulting in hospital admission or presentation to the emergency department. _____ Previous Study objectives: The researchers will perform a clinical trial to test whether treating patients with alcohol-related and metabolic-associated fatty liver cirrhosis with faecal microbiota transplantation (FMT) capsules vs placebo capsules will reduce the likelihood of them getting an infection by measuring the time it takes to develop an infection resulting in hospital admission.
Ethics approval(s)	Approved 16/03/2023, East of England – Cambridge South Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, United Kingdom; +44 (0)207 104 8084; cambridgesouth.rec@hra.nhs.uk), ref: 22/EE/0247
Health condition(s) or problem(s) studied	Infection and decompensation in patients with cirrhosis
Intervention	Randomisation: Patients will be randomised on a 1:1 basis to either FMT or placebo using the King's Clinical Trial Unit (KCTU) web-based randomisation system. Randomisation will be at the level of the individual using the method of block randomisation with varying block sizes, stratified by site. Intervention: Patients will be randomly allocated to two treatment arms: 1. Active treatment - patients assigned to this group will receive the active drug (FMT capsules) 2. The comparison or ‘control group’: Participants in this group will receive a ‘placebo’ treatment. The placebo will be a dummy capsule and will NOT contain any stool The FMT product contains 0.9% sodium chloride and 5% trehalose (cryoprotectant) as excipients. A minimum of 80 g of faeces from a single donor will be used to manufacture one batch of five capsules. Following lyophilisation, the material will be encapsulated in five size 0 delayed-release methylcellulose capsules (DRcaps™, Capsugel®, Livingston, UK). Placebo capsules will contain microcrystalline cellulose. The capsules for the FMT and placebo will be identical in appearance. The capsules are coloured Swedish orange, resulting in an opaque appearance through which the contents cannot be seen. FMT material will be fully traceable from donor to recipient. Aliquots of donor stool will be kept for 30 years to allow for future testing if required. The patients will need to take five capsules every 3 months. Patients will continue treatment for a total of 21 months or until they develop their first infection leading to hospital admission and will be followed up for a maximum of 2 years at different timepoints - baseline, 30 days (telephone call), 3, 6, 9, 12, 15, 18, 21 and 24 months. At each clinic visit, patients will receive five capsules of the medicine (either the FMT or the placebo) to be taken by mouth and swallowed with water or cordial.
Intervention type	Biological/Vaccine
Phase	Phase III
Drug / device / biological / vaccine name(s)	Faecal microbiota transplantation (FMT)
Primary outcome measure(s)	Current primary outcome(s) as of 13/02/2026: 1. Time to first infection resulting in presentation to the Emergency Department (ED) or admission into hospital with a confirmed infection 2. Decompensating episodes as defined in the criteria below: a. Resulting in presentation to the Emergency Department b. Resulting in hospital admission When the patients meet the primary endpoint, they do not receive further IMP or attend trial visits, but they will continue to be enrolled in the trial for the purposes of monitoring of other clinical endpoints, e.g. all-cause mortality and liver-related mortality. _____ Previous primary outcome(s): Time to the first infection resulting in hospital admission i.e., the date the patient is admitted to the hospital due to infection, collected using the King's Clinical Trials Unit Index Hospitalisation (Primary Endpoint) form administered by the research nurse at each clinic visit i.e, 3, 6, 9, 12, 15, 18, 21 and 24 months. When the patients meet the primary endpoint, they do not receive further IMP or attend trial visits, but they will continue to be enrolled in the trial for the purposes of monitoring of other clinical endpoints, e.g. all-cause mortality and liver-related mortality.
Key secondary outcome measure(s)	Current key secondary outcome(s) as of 13/02/2026: 1. Time to first infection resulting in hospitalisation over 24 month follow up period (former primary endpoint). 2. Incidence of decompensating events including hepatic encephalopathy, new-onset or worsening ascites or variceal bleeding over 24 month follow up period. 3. Incidence of all-cause infection over 24 month follow up period, including infections not resulting in hospitalisation. 4. Progression to ACLF (the development of one or more extrahepatic organ failures) 5. Infection rates and antibiotic usage following randomisation over 24 month follow up period. 6. Incidence of antimicrobial resistance (AMR) including skin and nose colonisation with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), extended-spectrum beta-lactamase-producing bacteria (ESBL), fluoroquinolone-resistant Gram-negative and carbapenem-resistant Enterobacteriales (over 24 month follow up period). 7. Hospitalisation rates (liver-related and all-cause), including the length of stay and admission to high dependency/intensive care (over 24 month follow up period). 8. Change in liver disease severity scores at 3-, 6-, 12- and 24-months post randomisation. 9. Change in quality of life (EQ-5D-5L score) at 3, 6, 12 and 24 months post-randomisation 10. All-cause mortality and liver-related mortality 11. Change in depression and anxiety scores using HADS at 3, 6, 12 and 24-months post-randomisation 12. Change in alcohol use disorder-related events in patients enrolled with alcohol-related cirrhosis as assessed by the alcohol-use disorders identification test (AUDIT score) at 3, 6, 12 and 24 months post randomisation, and urinary ethyl glucuronide/ethyl sulphate levels if tested as part of the standard of care. 13. Safety of FMT based on safety assessments including physical examination, clinical laboratory evaluation, vital signs and reported as adverse events (AEs) or serious adverse events (SAEs) over 24-month follow-up period. _____ Previous key secondary outcome(s): 1. Incidence of decompensating events including hepatic encephalopathy, new-onset ascites, variceal bleeding and spontaneous bacterial peritonitis, measured using study-specific laboratory analyses on blood, stool and urine samples at baseline, 3, 6 and 12 months 2. Progression to acute-on-chronic liver failure (ACLF) (the development of one or more organ failures) measured using study-specific laboratory analyses on blood, stool and urine samples at baseline, 3, 6 and 12 months 3. Infection rates and antibiotic usage collected using the concomitant medications log following randomisation 4. Incidence of AMR including skin and nose colonisation with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), extended-spectrum beta-lactamase-producing bacteria (ESBL), fluoroquinolone-resistant Gram-negative and carbapenem-resistant Enterobacteriales, measured using study-specific laboratory analyses on blood, stool and urine samples at baseline, 3, 6 and 12 months 5. Hospitalisation rates (liver-related and all-cause), including the length of stay and admission to high dependency/intensive care, collected using the King's Clinical Trials Unit Hospitalisation Log and patient medical notes at 3, 6, 9, 12, 15, 18, 21 and 24 months 6. Liver disease severity measured using the Child-Pugh, Model For End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) scores at baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months 7. Quality of life measured using the EQ-5D-5L questionnaire at baseline, 3, 6, 12 and 24 months 8. All-cause mortality and liver-related mortality collected from patient medical notes and adverse events log at day 30 over the telephone and thereafter at each clinic visit i.e., 3, 6, 9, 12, 15, 18, 21 and 24 months 9. Depression and anxiety measured using the Hospital Anxiety and Depression Scale (HADS) at baseline, 3, 6, 12 and 24 months 10. Alcohol use disorder-related events in patients enrolled with alcohol-related cirrhosis, measured using the alcohol-use disorders identification test (AUDIT questionnaire) at baseline, 3, 6, 12 and 24 months and urinary ethyl glucuronide/ethyl sulphate levels if tested as part of the standard of care 11. Faecal microbiome composition analysed by sequencing and metabolome analysis at baseline, 3, 6 and 12 months 12. Dietary habits measured using a study-specific dietary questionnaire developed by the team at baseline
Completion date	30/06/2028

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	18 Years
Upper age limit	120 Years
Sex	All
Target sample size at registration	300
Key inclusion criteria	Current key inclusion criteria as of 13/02/2026: 1. Age 18 years or over 2. Confirmed alcohol-related cirrhosis (ALD) or Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) or MetALD cirrhosis based on clinical, radiological and/or histological criteria 3. Model For End-Stage Liver Disease (MELD) score 8-16 4. Patients with alcohol-related cirrhosis who must have an active alcohol consumption on average ≤20 grams/day. 5. Patients must be deemed to have the capacity to consent _____ Previous key inclusion criteria: 1. Age 18 years or over 2. Confirmed alcohol-related cirrhosis or metabolic-associated fatty liver (MAFLD) cirrhosis based on clinical, radiological and/or histological criteria 3. Model For End-Stage Liver Disease (MELD) score 8-16 4. Patients with alcohol-related cirrhosis must have been abstinent for a minimum of 4 weeks prior to randomisation 5. Patients must be deemed to have the capacity to consent (if patients lose capacity during the trial a legal representative will be appointed on their behalf)
Key exclusion criteria	Current key exclusion criteria as of 13/02/2026: 1. Moderate, severe or life-threatening food allergy (e.g., peanut allergy) 2. Pregnancy or planned pregnancy. Urine testing will be performed at randomisation to rule out pregnancy in females 3. Breastfeeding 4. Patients treated for acute variceal bleeding, infection, overt hepatic encephalopathy, bacterial peritonitis or ACLF within 14 days prior to randomisation 5. Active alcohol consumption of >20 g/day (1 unit of alcohol contains 10 ml or 8 g of alcohol) 6. Had a previous liver transplant 7. Patients with inflammatory bowel disease 8. Patients with coeliac disease. 9. Patients with a history of prior gastrointestinal resection or surgery that could change the gut microbiome or result in bacterial overgrowth e.g. gastric bypass 10. Active malignancy including hepatocellular carcinoma 11. Patients with an expected life expectancy <6 months or listed for liver transplantation 12. Infected with HIV, hepatitis B or C (patients who have undetectable hepatitis B or C DNA/RNA can be recruited) 13. Patients who have received antibiotics or probiotics (excluding foodstuffs containing ‘live bacteria’ such as live yoghurts, kefir, fermented vegetables such as sauerkraut/kombucha or cheese) within 7 days prior to randomisation 14. Swallowing disorder, oral-motor dyscoordination or likely inability/unwillingness to ingest study medication 15. Patients who have received another investigational drug or device within 4 months prior to randomisation 16. Patients, who in the opinion of the PI, have a medical condition, or other relevant psychological, familial, or social factor that may jeopardise their health, compliance, or influence the trial integrity in any way. _____ Previous key exclusion criteria: 1. Severe or life-threatening food allergy (e.g., peanut allergy) 2. Pregnancy or planned pregnancy. Urine testing will be performed at randomisation to rule out pregnancy in females 3. Breastfeeding 4. Patients treated for acute variceal bleeding, infection, overt hepatic encephalopathy, bacterial peritonitis or ACLF within 14 days prior to randomisation 5. Active alcohol consumption of >20 g/day (1 unit of alcohol contains 10 ml or 8 g of alcohol) 6. Had a previous liver transplant 7. Patients with inflammatory bowel disease 8. Patients with coeliac disease. 9. Patients with a history of prior gastrointestinal resection such as gastric bypass 10. Active malignancy including hepatocellular carcinoma 11. Patients with an expected life expectancy <6 months or listed for liver transplantation 12. Infected with HIV, hepatitis B or C (patients who have undetectable hepatitis B or C DNA/RNA can be recruited) 13. Patients who have received antibiotics or probiotics (excluding foodstuffs containing ‘live bacteria’ such as live yoghurts, kefir, fermented vegetables such as sauerkraut/kombucha or cheese) within 7 days prior to randomisation 14. Swallowing disorder, oral-motor dyscoordination or likely inability/unwillingness to ingest study medication 15. Patients who have received another investigational drug or device within 4 months prior to randomisation
Date of first enrolment	21/06/2023
Date of final enrolment	31/12/2026

Locations

Countries of recruitment

United Kingdom
England
Scotland

Study participating centres

King's College Hospital

Institute of Liver Studies
Denmark Hill
London
SE5 9RS
England

St Georges Hospital

Blackshaw Road
London
SW17 0QT
England

St Mary's Hospital

Praed St
London
W2 1NY
England

St James University Hospital

Leeds Institute for Data Analytics
Room 6.1, Level 6 Clinical Sciences Building
University of Leeds
Beckett Street
Leeds
LS9 7TF
England

Freeman Road Hospital

Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
England

Queens Medical Centre

Nottingham University Hospital
Derby Road
Nottingham
NG7 2UH
England

Glasgow Royal Infirmary

84 Castle Street
Glasgow
G4 0SF
Scotland

Ninewells Hospital

Ninewells Avenue
Dundee
DD1 9SY
Scotland

Queen Elizabeth Hospital

Sherriff Hill
Gateshead
NE9 6SX
England

Royal Derby Hospital

Uttoxeter Road
Derby
DE22 3NE
England

Royal Bournemouth Hospital

Castle Lane East
Bournemouth
BH7 7DW
England

Queen Elizabeth University Hospital

1345 Govan Road
Glasgow
G51 4TF
Scotland

Hull Royal Infirmary

Anlaby Road
Hull
HU3 2JZ
England

Derriford Hospital

Derriford Road
Plymouth
PL6 8DH
England

Bristol Royal Infirmary

Upper Maudlin Street
Bristol
BS2 8BJ
England

Southmead Hospital

Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
England

University Hospital Hairmyres

Eaglesham Road
East Kilbride
G75 8RG
Scotland

Basildon University Hospital

Nethermayne
Basildon
SS16 5NL
England

Broomfield University Hospital

Broomfield Hospital
Court Road
Chelmsford
CM1 7ET
England

Raigmore Hospital

Old Perth Rd
Inverness
IV2 3UJ
Scotland

Torbay Hospital

Newton Road
Torquay
TQ2 7AA
England

University Hospital Southampton

Tremona Road
Southampton
SO16 6YD
England

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Published as a supplement to the results publication
IPD sharing plan	The datasets generated and/or analysed during the current study will be published as a supplement to the results publication

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

13/02/2026: The following changes were made to the study record:
1. The Study objectives were changed.
2. The Health condition(s) or problem(s) studied was changed from "Infection in patients with cirrhosis" to "Infection and decompensation in patients with cirrhosis".
3. The primary outcome(s) were changed.
4. The key secondary outcome(s) were changed.
5. The key inclusion criteria were changed.
6. The key exclusion criteria were changed.
7. The date of final enrolment was changed from 30/01/2026 to 31/12/2026
8. The study participating centres were updated.
9. The plain English summary was updated to reflect these changes.
22/11/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/11/2024 to 30/01/2026.
2. The overall end date was changed from 31/03/2026 to 30/06/2028.
3. The intention to publish date was changed from 30/04/2026 to 30/07/2028.
4. The plain English summary was updated to reflect these changes.
5. The clinicaltrials.gov number was added.
30/01/2024: The following changes were made:
1. The recruitment end date was changed from 30/11/2025 to 30/11/2024.
2. The study participating centre at Royal Liverpool University Hospital was removed.
3. The study participating centre at Royal Bournemouth Hospital was added.
18/07/2023: The following changes have been made:
1. The recruitment start date was changed from 01/02/2023 to 21/06/2023.
2. The public contact was updated.
3. The ethics approval was added.
4. The individual participant data (IPD) sharing plan was added.
07/11/2022: Ethics approval details added, the recruitment start date was changed from 01/11/2022 to 01/02/2023.
05/05/2022: The recruitment start date has been changed from 01/04/2022 to 01/11/2022.
04/04/2022: The intention to publish date has been corrected from 30/04/2022 to 30/04/2026.
24/03/2022: Trial's existence confirmed by the NIHR.