PROMISE: a PROspective randomised double-blind parallel group placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis over 24 months—study protocol for a clinical trial
10 affiliations
- 1Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Foundation for Liver Research and King’s College Hospital, London, UK
- 2King’s Clinical Trials Unit, King’s College London, London, UK
- 3Centre for Clinical Infection and Diagnostics Research (CIDR), King’s College London and Guy’s & St. Thomas’ NHS Foundation Trust, London, UK
- 4Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- 5King’s Health Partners Clinical Trials Office, King’s College London, London, UK
- 6Patient and Public Representatives, London, UK
- 7British Liver Trust, Venta Court, Winchester, UK
- 8Department of Hepatology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
- 9Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- 10Infection Clinical Academic Group, City St. George’s University of London, London, UK
Abstract
Background: Patients with cirrhosis have reduced gut bacterial diversity and a gut microbiota dominated by pathobionts. These changes, coupled with increased gut permeability and bacterial translocation, increase susceptibility to infection and death. There is also considerable concern that high antimicrobial exposure in the cirrhotic population drives the development of antimicrobial resistance (AMR). We previously performed a randomised feasibility trial of endoscopically administered jejunal faecal microbiota transplant (FMT) slurry derived from stringently screened donors, and showed it to be safe and well-tolerated in patients with cirrhosis (PROFIT Trial: NCT02862249). FMT was associated with reduced enteropathogenic bacteria in the gut, augmented ammonia excretion, ameliorated systemic inflammation, and enhanced innate immune responses to pathogen challenge. The trial was not powered to detect differences in clinical outcomes. The PROMISE study will evaluate the efficacy of lyophilised encapsulated FMT to reduce infection, decompensating events and mortality in patients with cirrhosis secondary to alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and metabolic dysfunction and alcohol-related liver disease (MetALD).
Methods: The PROMISE study is a phase 3 multicentre, randomised, double-blinded, placebo-controlled trial that will evaluate encapsulated lyophilised FMT in 300 participants with ALD, MetALD or MASLD cirrhosis (Model for End-Stage Liver Disease Sodium (MELD-Na) score 8–16). Participants will be randomly allocated (1:1) to receive FMT or matched placebo capsules every 91 days for 21 months, with 24-month follow-up. The primary endpoint is time-to-infection or decompensating event resulting in presentation to the emergency department or hospitalisation.
Secondary endpoints include all hepatic decompensation, all-cause infection, antibiotic usage, incidence of AMR, hospitalisation rates, liver disease severity scores, quality of life scores, Hospital Anxiety and Depression Scale score (HADS), alcohol use, and mortality. Mechanistic endpoints include quantification of plasma bacterial DNA, plasma and faecal cytokines/biomarkers, plasma and faecal metabolome, faecal proteome, faecal microbiome composition and diversity (including resistome) and monocyte and mucosal-associated invariant T (MAIT) cell frequency, phenotype and function. Recruitment commenced in June 2023. Results will be disseminated via peer-reviewed journals, international conferences and patient support groups.
Discussion: The PROMISE study will assess the efficacy and evaluate the mechanisms of action of FMT in patients with ALD, MASLD and MetALD cirrhosis. FMT may provide an alternative non-antibiotic treatment for these patients through ecological reconstitution of microbial balance.
Trial registration: ISRCTN, ISRCTN17863382. Registered on 25th March 2022, https://www.isrctn.com/ISRCTNISRCTN17863382. ClinicalTrials.gov NCT06461208. Registered on 4th June 2024, https://clinicaltrials.gov/study/NCT06461208#study-overview.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13063-026-09914-x.
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BibTeX
@article{kronsten2026promise,
title = {{PROMISE: a PROspective randomised double-blind parallel group placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis over 24 months—study protocol for a clinical trial}},
author = {Victoria T. Kronsten and Yevedzo Ntuli and Ellis Kobina Paintsil and Charlotte A. Woodhouse and Thomas H. Tranah and Sue Cheung and Daryl Hagan and Blair Merrick and Angela Cape and Francesca Maher and Kirin Sultana and Desiree Prossomariti and Steven Rodrigues and Christine Masterson and Vanessa Hebditch and Ane Zamalloa and Benjamin H. Mullish and Arjuna Singanayagam and Vishal C. Patel and Mark R. Thursz and Victoria T. Kronsten and Victoria T. Kronsten and Yevedzo Ntuli and Charlotte A. Woodhouse and Ane Zamalloa and Benjamin H. Mullish and Arjuna Singanayagam and Vishal C. Patel and Mark R. Thursz and Gavin Wright and Manuel Jasper and Tahir Khan and Syeda Amber Ali and Sarah Fairclough and Bushena Miyesa and Michael Villaruel and Princess Gabiana and Keval Naik and Caroline Fox and Miranda Forsey and Prem Karthikeyan and Jennifer Child and Yvonne Lester and Gautham Appanna and Hannah Donnelly and Alice Lagnado and Robbie Adamson and Joanne Elliot and Gifthy Perez and Rose Fyfe-Beedell and Siby Varghese and Chiaki Shioi and Bindu Mary Jinesh and Shannah O’Sullivan and Hannah Whitehouse and Eunice Akintemi and Matthew Cramp and Glen Marsh and Angela Downing and Gabriella Smallwood},
journal = {Trials},
year = {2026},
month = jul,
doi = {10.1186/s13063-026-09914-x},
url = {https://doi.org/10.1186/s13063-026-09914-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PROMISE: a PROspective randomised double-blind parallel group placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis over 24 months—study protocol for a clinical trial
AU - Victoria T. Kronsten
AU - Yevedzo Ntuli
AU - Ellis Kobina Paintsil
AU - Charlotte A. Woodhouse
AU - Thomas H. Tranah
AU - Sue Cheung
AU - Daryl Hagan
AU - Blair Merrick
AU - Angela Cape
AU - Francesca Maher
AU - Kirin Sultana
AU - Desiree Prossomariti
AU - Steven Rodrigues
AU - Christine Masterson
AU - Vanessa Hebditch
AU - Ane Zamalloa
AU - Benjamin H. Mullish
AU - Arjuna Singanayagam
AU - Vishal C. Patel
AU - Mark R. Thursz
AU - Victoria T. Kronsten
AU - Victoria T. Kronsten
AU - Yevedzo Ntuli
AU - Charlotte A. Woodhouse
AU - Ane Zamalloa
AU - Benjamin H. Mullish
AU - Arjuna Singanayagam
AU - Vishal C. Patel
AU - Mark R. Thursz
AU - Gavin Wright
AU - Manuel Jasper
AU - Tahir Khan
AU - Syeda Amber Ali
AU - Sarah Fairclough
AU - Bushena Miyesa
AU - Michael Villaruel
AU - Princess Gabiana
AU - Keval Naik
AU - Caroline Fox
AU - Miranda Forsey
AU - Prem Karthikeyan
AU - Jennifer Child
AU - Yvonne Lester
AU - Gautham Appanna
AU - Hannah Donnelly
AU - Alice Lagnado
AU - Robbie Adamson
AU - Joanne Elliot
AU - Gifthy Perez
AU - Rose Fyfe-Beedell
AU - Siby Varghese
AU - Chiaki Shioi
AU - Bindu Mary Jinesh
AU - Shannah O’Sullivan
AU - Hannah Whitehouse
AU - Eunice Akintemi
AU - Matthew Cramp
AU - Glen Marsh
AU - Angela Downing
AU - Gabriella Smallwood
PY - 2026
DA - 2026/07/31
JO - Trials
DO - 10.1186/s13063-026-09914-x
UR - https://doi.org/10.1186/s13063-026-09914-x
AB - Background: Patients with cirrhosis have reduced gut bacterial diversity and a gut microbiota dominated by pathobionts. These changes, coupled with increased gut permeability and bacterial translocation, increase susceptibility to infection and death. There is also considerable concern that high antimicrobial exposure in the cirrhotic population drives the development of antimicrobial resistance (AMR). We previously performed a randomised feasibility trial of endoscopically administered jejunal faecal microbiota transplant (FMT) slurry derived from stringently screened donors, and showed it to be safe and well-tolerated in patients with cirrhosis (PROFIT Trial: NCT02862249). FMT was associated with reduced enteropathogenic bacteria in the gut, augmented ammonia excretion, ameliorated systemic inflammation, and enhanced innate immune responses to pathogen challenge. The trial was not powered to detect differences in clinical outcomes. The PROMISE study will evaluate the efficacy of lyophilised encapsulated FMT to reduce infection, decompensating events and mortality in patients with cirrhosis secondary to alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and metabolic dysfunction and alcohol-related liver disease (MetALD). Methods: The PROMISE study is a phase 3 multicentre, randomised, double-blinded, placebo-controlled trial that will evaluate encapsulated lyophilised FMT in 300 participants with ALD, MetALD or MASLD cirrhosis (Model for End-Stage Liver Disease Sodium (MELD-Na) score 8–16). Participants will be randomly allocated (1:1) to receive FMT or matched placebo capsules every 91 days for 21 months, with 24-month follow-up. The primary endpoint is time-to-infection or decompensating event resulting in presentation to the emergency department or hospitalisation. Secondary endpoints include all hepatic decompensation, all-cause infection, antibiotic usage, incidence of AMR, hospitalisation rates, liver disease severity scores, quality of life scores, Hospital Anxiety and Depression Scale score (HADS), alcohol use, and mortality. Mechanistic endpoints include quantification of plasma bacterial DNA, plasma and faecal cytokines/biomarkers, plasma and faecal metabolome, faecal proteome, faecal microbiome composition and diversity (including resistome) and monocyte and mucosal-associated invariant T (MAIT) cell frequency, phenotype and function. Recruitment commenced in June 2023. Results will be disseminated via peer-reviewed journals, international conferences and patient support groups. Discussion: The PROMISE study will assess the efficacy and evaluate the mechanisms of action of FMT in patients with ALD, MASLD and MetALD cirrhosis. FMT may provide an alternative non-antibiotic treatment for these patients through ecological reconstitution of microbial balance. Trial registration: ISRCTN, ISRCTN17863382. Registered on 25th March 2022, https://www.isrctn.com/ISRCTNISRCTN17863382. ClinicalTrials.gov NCT06461208. Registered on 4th June 2024, https://clinicaltrials.gov/study/NCT06461208#study-overview. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13063-026-09914-x.
SN - 1745-6215
ER -