{
  "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).\n\nMethods: 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.\n\nSecondary 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.\n\nDiscussion: 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.\n\nTrial 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.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13063-026-09914-x.",
  "abstract_shown": true,
  "affiliations": [
    "Roger 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",
    "King’s Clinical Trials Unit, King’s College London, London, UK",
    "Centre for Clinical Infection and Diagnostics Research (CIDR), King’s College London and Guy’s & St. Thomas’ NHS Foundation Trust, London, UK",
    "Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK",
    "King’s Health Partners Clinical Trials Office, King’s College London, London, UK",
    "Patient and Public Representatives, London, UK",
    "British Liver Trust, Venta Court, Winchester, UK",
    "Department of Hepatology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK",
    "Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK",
    "Infection Clinical Academic Group, City St. George’s University of London, London, UK"
  ],
  "article_type": "research article",
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  "author_total": 184,
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  "bibtex": "https://research.draconitic.com/paper/9e5e2cnydrg0q.bib",
  "cited_by": 0,
  "doi": "10.1186/s13063-026-09914-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711809/",
  "id": "9e5e2cnydrg0q",
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  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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  "native_subjects": [
    [
      "heading",
      "Study Protocol"
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      "openalex",
      "2721|Liver Disease and Transplantation"
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  "openalex": "W7171972543",
  "pdf_url": null,
  "pmcid": "PMC13711809",
  "pmid": "42947250",
  "published": "2026-07-31",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/9e5e2cnydrg0q.ris",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1745-6215",
      "subfield": "clinical-trials"
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  "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",
  "title_text": "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",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:31Z",
  "url": "https://research.draconitic.com/paper/9e5e2cnydrg0q",
  "venue": "Trials",
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