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

NCT06461208 | Recruiting Phase 3 DMC

• 4 other identifiers: 10048222022-000300-35NIHREME130730ISRCTN17863382
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Liver Cirrhosis

Keywords

Fatty Liver Alcoholic; Alcohol-related Liver Disease; Metabolic dysfunction-Associated Steatotic Liver Disease; Liver Cirrhosis; MASLD; MASLD-ALD overlap cirrhosis; ALD; Faecal Microbiota Transplant; Metabolic Fatty Liver Disease; Fatty Liver Disease; Gut Microbiota; Cirrhosis; PROMISE; MetALD; Liver Decompensation; Hepatic Encephalopathy; Infection; New Onset Ascites; Variceal Bleeding

Outcome Measures

Primary Outcomes (2)

• Defined infection resulting in presentation to the emergency department or hospital admission (time to event)

  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)

  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 Outcomes (21)

• Time to first infection resulting in hospitalisation over 24 month follow up period

  Screening - End of Visit (Month 24)

• Incidence of decompensating events

  Screening - End of Visit (Month 24)

• All-cause infection

  Screening - End of Visit (Month 24)

• Progression to ACLF (Acute on Chronic Liver Failure) i.e. the development of one or more organ failure

  Screening - End of Visit (Month 24)

• Incidence of antibiotic usage

  Screening - End of Visit (Month 24)

Study Arms (2)

Encapsulated FMT

EXPERIMENTAL

Drug: Encapsulated FMT

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Encapsulated FMT DRUG

Encapsulated Faecal Microbiota Transplant

Encapsulated FMT

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Moderate, severe or life-threatening food allergy (e.g., peanut allergy)
• Pregnancy or planned pregnancy\*. Urine testing will be performed at screening to rule out pregnancy in females.
• Breast-feeding
• Patients treated for acute variceal bleeding, infection, overt hepatic encephalopathy, bacterial peritonitis or ACLF within 14 days prior to randomisation.
• Active alcohol consumption of \>20 grams/day \[1 unit of alcohol contains 10mLs or 8g of alcohol\]
• Had a previous liver transplant
• Patients with inflammatory bowel disease.
• Patients with coeliac disease.
• 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
• Active malignancy including hepatocellular carcinoma
• Patients with an expected life expectancy \<6 months or listed for liver transplantation
• Infected with HIV, hepatitis B or C \[patients who have undetectable hepatitis B or C DNA/RNA can be recruited\].
• 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.
• Swallowing disorder, oral-motor dyscoordination or likely inability/unwillingness to ingest study medication.
• Patients who have received another investigational drug or device within 4 months prior to randomisation.

Sponsors & Collaborators

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

Study Sites (23)

Basildon University Hospital

Basildon, SS16 5NL, United Kingdom

RECRUITING

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

RECRUITING

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

RECRUITING

Bristol Royal Infirmary

Bristol, BS2 8HW, United Kingdom

RECRUITING

Broomfield Hospital

Chelmsford, CM1 7ET, United Kingdom

RECRUITING

Royal Derby Hospital

Derby, DE22 3NE, United Kingdom

RECRUITING

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Gateshead, NE9 6SX, United Kingdom

RECRUITING

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

RECRUITING

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

RECRUITING

University Hospital Hairmyres

Glasgow, G75 8RG, United Kingdom

RECRUITING

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

RECRUITING

Raigmore Hospital

Inverness, IV2 3UJ, United Kingdom

RECRUITING

St. James University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

RECRUITING

St. George's University Hospital NHS Foundation Trust

London, SW17 0QT, United Kingdom

RECRUITING

St. Mary's Hospital

London, W2 1NY, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Royal Gwent Hospital

Newport, NP20 2UB, United Kingdom

WITHDRAWN

Queen's Medical Centre

Nottingham, NG7 2UH, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

RECRUITING

University Hospital Southampton

Southampton, SO16 6YD, United Kingdom

RECRUITING

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Fatty Liver, Alcoholic; Non-alcoholic Fatty Liver Disease; Fibrosis; Hepatic Insufficiency; Hepatic Encephalopathy; Infections

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Liver Failure; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Sue Cheung

CONTACT

020 7848 0532; PROMISE@kcl.ac.uk

Debbie Shawcross

CONTACT

020 3299 3713; debbie.shawcross@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants, Chief Investigator, Site Principal Investigators and outcome assessors will be fully blinded throughout the trial. The site pharmacy trials team and the nurse administering the treatment will be unblinded to a patients treatment allocation. The senior statistician will also be fully blinded, but the junior statistician will be unblinded from the 1st DMC meeting with data onwards.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomised 1:1 to FMT or placebo.

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 14, 2024
• Study Start: June 21, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: February 24, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (23)