A PROspective Faecal MIcrobiota tranSplantation Trial to Improve outcomEs in Patients With Cirrhosis
NCT Number: NCT06461208
Acronym: PROMISE
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Liver Cirrhosis
Interventions: DRUG: Encapsulated FMT|OTHER: Placebo
Sponsor: King's College London
Collaborators: St George's, University of London|Guy's and St Thomas' NHS Foundation Trust|Imperial College London|King's College Hospital NHS Trust|BRITISH LIVER TRUST
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 300
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2023-06-21
Completion Date: 2027-04-30
Locations: Royal Bournemouth Hospital, Bournemouth, BH7 7DW, United Kingdom|Southmead Hospital, Bristol, BS10 5NB, United Kingdom|Bristol Royal Infirmary, Bristol, BS2 8HW, United Kingdom|Royal Derby Hospital, Derby, DE22 3NE, United Kingdom|Ninewells Hospital, Dundee, DD1 9SY, United Kingdom|Queen Elizabeth Hospital, Gateshead, NE9 6SX, United Kingdom|Queen Elizabeth University Hospital, Glasgow, G51 4TF, United Kingdom|Hull Royal Infirmary, Hull, HU3 2JZ, United Kingdom|St. James University Hospital, Leeds, LS9 7TF, United Kingdom|King's College Hospital NHS Foundation Trust, London, SE5 9RS, United Kingdom|St. George's University Hospital NHS Foundation Trust, London, SW17 0QT, United Kingdom|St. Mary's Hospital, London, W2 1NY, United Kingdom|Freeman Hospital, Newcastle Upon Tyne, NE7 7DN, United Kingdom|Royal Gwent Hospital, Newport, NP20 2UB, United Kingdom|Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom|Derriford Hospital, Plymouth, PL6 8DH, United Kingdom

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.

Primary Outcome Measures: Defined infection resulting in hospital admission, 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 hospitalisation., From date of randomisation until the date of first hospitlisation, assessed up to Month 24.
Secondary Outcome Measures: Incidence of decompensating events, All types of decompensating events will be included:

i. hepatic encephalopathy, ii. new-onset ascites, iii. variceal bleeding and iv. spontaneous bacterial peritonitis., 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)|All-cause culture-confirmed infection, Screening - End of Visit (Month 24)|Incidence of antibiotic usage, Screening - End of Visit (Month 24)|Occurrence of AMR (Anti-Microbial Resistance), (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)|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., Screening - End of Visit (Month 24)|Change in liver disease severity scores, 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, 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, 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, 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), 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., 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), 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., Screening - End of Visit (Month 24)