A PROspective Faecal MIcrobiota tranSplantation Trial to Improve outcomEs in Patients With Cirrhosis (PROMISE)

February 19, 2026 updated by: King's College London

PROMISE Trial: 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

A feasibility trial called PROFIT has previously shown that FMT administered endoscopically into the jejunum in patients with cirrhosis is safe and feasible and have identified some potential mechanisms of action that warrant further interrogation. The aim of the PROMISE Trial is to evaluate the efficacy and mechanisms of action of encapsulated FMT (versus placebo) to reduce infection and mortality in patients with alcohol-related and metabolic dysfunction-Associated Steatotic Liver (MASLD) cirrhosis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

There is an evolving crisis of chronic liver disease (CLD) in the UK and it is the only major chronic disease which is on the rise. The advanced stages of CLD, known as cirrhosis (a hardening and scarring of the liver), is the third biggest cause of death and loss of working life years behind heart disease and self-harm. People die from cirrhosis young with more than 1 in 10 in their 40s.

Patients with cirrhosis are very susceptible to infections, antibiotics become ineffective and patients may become infected with 'super bugs'. There is an urgent need for antibiotic-free approaches. The body contains trillions of microscopic organisms called bacteria which play an important role in keeping us healthy. Many of these bacteria live within our bowel and help our immune system fight infection. There are increased numbers of 'unfriendly' bowel bacteria in patients with cirrhosis which emit substances that are harmful to health and disrupt the immune system.

It could be beneficial to replace the unfriendly bowel bacteria in patients with cirrhosis with bacteria donated from a healthy person by performing a type of bowel bacteria transplant (known as faecal microbiota transplantation or FMT). The PROFIT trial was recently performed as a preliminary trial of FMT which was placed into the bowel with the help of a flexible camera (endoscopy). The study showed FMT was safe with no serious side effects, but patients told us they would prefer to take tablets rather than have an endoscopy. The chief investigator and her team have therefore made a capsule which contains dried stool from a healthy donor. Participants will need to take 5 of these capsules to achieve the same dose.

The PROMISE clinical trial is to test whether treating patients with FMT capsules will reduce the likelihood of them getting an infection by measuring the time it takes to develop an infection resulting in hospital admission. This will be compared to a 'dummy' capsule that contains no FMT (placebo). Patients will be selected at random to have FMT treatment or placebo and both the study team and the patients will not know which treatment they are taking. Participants will need to take 5 capsules every 3-months. Participants 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.

This study will also examine if having FMT will reduce the side effects of cirrhosis and if it has beneficial effects on the liver and immune system. The investigator team will study whether it 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.

The World Health Organisation describes the resistance of bacteria to the effects of antibiotics as one of the biggest threats to global health. The discovery of new antibiotics has not kept pace. The government's white paper proposes a 5-year plan to tackle resistance to antibiotics. Consultation with our patient co-applicant, patient advisory group, The British Liver Trust and Guts UK Charity have highlighted recurrent hospitalisation, over-use of antibiotics and fear of acquiring a 'super-bug' as being important priorities to patients. The results and study findings will be published in conjunction with patient support groups, the wider media and the NHS. The investigator will ensure the research impacts on the management of patients with CLD and shapes policy and guideline development.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Basildon, United Kingdom, SS16 5NL
        • Recruiting
        • Basildon University Hospital
        • Principal Investigator:
          • Gavin Wright
        • Contact:
      • Bournemouth, United Kingdom, BH7 7DW
        • Recruiting
        • Royal Bournemouth Hospital
        • Contact:
        • Principal Investigator:
          • Safa Al-Shamma
      • Bristol, United Kingdom, BS2 8HW
      • Bristol, United Kingdom, BS10 5NB
        • Recruiting
        • Southmead Hospital
        • Contact:
        • Principal Investigator:
          • Zeino Zeino
      • Chelmsford, United Kingdom, CM1 7ET
        • Recruiting
        • Broomfield Hospital
        • Principal Investigator:
          • Gavin Wright
        • Contact:
        • Sub-Investigator:
          • Keval Naik
      • Derby, United Kingdom, DE22 3NE
        • Recruiting
        • Royal Derby Hospital
        • Contact:
        • Principal Investigator:
          • Nicholas Taylor
      • Dundee, United Kingdom, DD1 9SY
        • Recruiting
        • Ninewells Hospital
        • Contact:
        • Principal Investigator:
          • Ruairi Lynch
      • Gateshead, United Kingdom, NE9 6SX
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
        • Principal Investigator:
          • Dina Mansour
      • Glasgow, United Kingdom, G51 4TF
        • Recruiting
        • Queen Elizabeth University Hospital
        • Contact:
        • Principal Investigator:
          • Rachael Swann
      • Glasgow, United Kingdom, G75 8RG
      • Glasgow, United Kingdom, G4 0SF
        • Recruiting
        • Glasgow Royal Infirmary
        • Principal Investigator:
          • Rachael Swann
        • Contact:
      • Hull, United Kingdom, HU3 2JZ
        • Recruiting
        • Hull Royal Infirmary
        • Contact:
        • Principal Investigator:
          • Lynse Corless
      • Inverness, United Kingdom, IV2 3UJ
        • Recruiting
        • Raigmore Hospital
        • Contact:
        • Principal Investigator:
          • Sebastian Wallace
      • Leeds, United Kingdom, LS9 7TF
        • Recruiting
        • St. James University Hospital
        • Contact:
        • Principal Investigator:
          • Ian Rowe
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Vishal Patel
      • London, United Kingdom, W2 1NY
        • Recruiting
        • St. Mary's Hospital
        • Principal Investigator:
          • Mark Thursz
        • Contact:
      • London, United Kingdom, SW17 0QT
        • Recruiting
        • St. George's University Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Arjuna Singayagam
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Recruiting
        • Freeman Hospital
        • Contact:
        • Principal Investigator:
          • Steve Masson
      • Newport, United Kingdom, NP20 2UB
        • Withdrawn
        • Royal Gwent Hospital
      • Nottingham, United Kingdom, NG7 2UH
        • Recruiting
        • Queen's Medical Centre
        • Contact:
        • Principal Investigator:
          • Guru Aithal Prasad
      • Plymouth, United Kingdom, PL6 8DH
        • Recruiting
        • Derriford Hospital
        • Principal Investigator:
          • Matthew Cramp
        • Contact:
      • Southampton, United Kingdom, so16 6yd
        • Recruiting
        • University Hospital Southampton
        • Principal Investigator:
          • Janisha Patel
        • Contact:
      • Torquay, United Kingdom, TQ2 7AA
        • Recruiting
        • Torbay Hospital
        • Principal Investigator:
          • James Neale
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥ 18 years
  2. Confirmed Alcohol-related (ALD) or Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) or MetALD cirrhosis based on clinical, radiological and/or histological criteria.
  3. MELD score 8-16
  4. Patients with alcohol-related cirrhosis who must have an active alcohol consumption on average ≤20 grams/day [1 unit of alcohol contains 10mLs or 8g of alcohol].
  5. Patients must be deemed to have the capacity to provide written informed consent to participate.

Exclusion Criteria:

  1. Moderate, severe or life-threatening food allergy (e.g., peanut allergy)
  2. Pregnancy or planned pregnancy*. Urine testing will be performed at screening to rule out pregnancy in females.
  3. Breast-feeding
  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 grams/day [1 unit of alcohol contains 10mLs or 8g 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 food stuffs 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
The placebo product contains microcrystalline methylcellulose. It is supplied as a size 0, Swedish Orange Delayed-Release capsule (DRCap) and provides a complete match with regards to the appearance (e.g., dimensions, colour) to the FMT capsules.
Experimental: Encapsulated FMT
Drug: Encapsulated FMT
Encapsulated Faecal Microbiota Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Defined infection resulting in presentation to the emergency department or hospital admission (time to event)
Time Frame: From date of randomisation until the date of first hospitlisation, assessed up to Month 24.
To evaluate the efficacy of encapsulated FMT to reduce the susceptibility of infection in patients with cirrhosis measured by the time to first infection resulting in presentation to the emergency department or hospitalisation.
From date of randomisation until the date of first hospitlisation, assessed up to Month 24.
Defined Decompensation episode resulting in presentation to emergency department or hospital admission (time to event)
Time Frame: From date of randomisation until the date of first hospitalisation, assessed up to Month 24.

Decompensation episodes of the following:

  1. New onset moderate or large volume ascites requiring diuretic therapy or paracentesis
  2. Variceal Bleeding confirmed following emergency endoscopy or on CT angiography suggestive of bleeding elsewhere in the gastrointestinal tract as a consequence of portal hypertension.
  3. Overt hepatic encephalopathy (Westhaven Criteria grade 2-4)
From date of randomisation until the date of first hospitalisation, assessed up to Month 24.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression to ACLF (Acute on Chronic Liver Failure) i.e. the development of one or more organ failure
Time Frame: Screening - End of Visit (Month 24)
Screening - End of Visit (Month 24)
Incidence of antibiotic usage
Time Frame: Screening - End of Visit (Month 24)
Screening - End of Visit (Month 24)
Hospitalisation rates (liver-related and all-cause) (time to event) including the length of stay (time to discharge among hospitalised participants) and admission to high dependency/intensive care.
Time Frame: Screening - End of Visit (Month 24)
Screening - End of Visit (Month 24)
Change in liver disease severity scores
Time Frame: Screening - End of Visit (Month 24)
Child Pugh Score Score range: Min 5 - Max 15 (The higher score, the more worse outcome)
Screening - End of Visit (Month 24)
Change in liver disease severity scores
Time Frame: Screening - End of Visit (Month 24)
MELD Score (Model for End stage Liver Disease) Score range: Min 6 - Max 40 (The higher score, the more worse outcome)
Screening - End of Visit (Month 24)
Change in liver disease severity scores
Time Frame: Screening - End of Visit (Month 24)
UKELD Score (UK for End stage Liver Disease) Score range: Min 40 - Max 80 (The higher score, the more worse outcome)
Screening - End of Visit (Month 24)
Change in quality of life (EQ-5D-5L) scores
Time Frame: Screening - End of Visit (Month 24)
EQ-5D-5L Score (EuroQol-5 Dimension- 5 Levels) Score range: Min 11111 - Max 55555 (The higher score, the more worse outcome)
Screening - End of Visit (Month 24)
Change in depression and anxiety scores (using HADS)
Time Frame: Screening - End of Visit (Month 24)
HADS Score (Hospital Anxiety Depression Scale) Score range: Min 0 - Max 21 (The higher score, the more worse outcome) Data for anxiety and depression to be cateogorised separately.
Screening - End of Visit (Month 24)
All-cause mortality and liver-related mortality.
Time Frame: Screening - End of Visit (Month 24)
Screening - End of Visit (Month 24)
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)
Time Frame: Screening - End of Visit (Month 24)
AUDIT Score (Alcohol Use Disorder Identification Test) Score range: Min 0 - Max 40 (The higher score, the more worse outcome)
Screening - End of Visit (Month 24)
Change in urinary ethyl glucuronide/ethyl sulphate levels if tested as part of the standard of care.
Time Frame: Screening - End of Visit (Month 24)
Screening - End of Visit (Month 24)
Time to first infection resulting in hospitalisation over 24 month follow up period
Time Frame: Screening - End of Visit (Month 24)
(former primary endpoint)
Screening - End of Visit (Month 24)
Incidence of decompensating events
Time Frame: Screening - End of Visit (Month 24)

All types of decompensating events will be included:

  1. hepatic encephalopathy
  2. new-onset or worsening ascites
  3. variceal bleeding
Screening - End of Visit (Month 24)
All-cause infection
Time Frame: Screening - End of Visit (Month 24)
Including infections not resulting in hospitalisation
Screening - End of Visit (Month 24)
Incidence of AMR (Anti-Microbial Resistance)
Time Frame: Screening - End of Visit (Month 24)
(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 linezolid-resistant Enterococci (LRE).
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on assessments including weight in kg
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on safety assessments including blood pressure (mmHg)
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on safety assessments including heart rate in bpm
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on safety assessments, Oxygen Saturation in %
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on safety assessments, measured temperatures in degrees celcius
Screening - End of Visit (Month 24)
Safety of FMT
Time Frame: Screening - End of Visit (Month 24)
Based on safety assessments including evaluation of reported adverse events or serious adverse events
Screening - End of Visit (Month 24)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King's College London

Collaborators

King's College Hospital NHS Trust
Imperial College London
Guy's and St Thomas' NHS Foundation Trust
St George's Healthcare NHS Trust
BRITISH LIVER TRUST

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2023

Primary Completion (Estimated)

January 31, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

June 4, 2024

First Submitted That Met QC Criteria

June 11, 2024

First Posted (Actual)

June 14, 2024

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1004822
  • 2022-000300-35 (EudraCT Number)
  • NIHREME130730 (Other Grant/Funding Number: NIHR EME)
  • ISRCTN17863382 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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