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This is a phase III, multicenter, double-blind, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of Fecal Microbiota Transplantation (FMT) from healthy subjects to patients with decompensated cirrhosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fecal Microbiome Transplantation (FMT) | Experimental | A first dose of 24 capsules of FMT at baseline and a second dose of 24 capsules of FMT at 3 months. Each dose (24 capsules) contains approximately 50g of stool. |
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| FMT Placebo | Placebo Comparator | A first dose of 24 capsules of FMT placebo at baseline and a second dose of 24 capsules of FMT placebo at 3 months. Each dose (24 capsules) contains in total 6 g of microcrystalline cellulose or equivalent. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal Microbiome Transplantation (FMT) | Drug | Two doses: First dose: 24 capsules of FMT at baseline. Second dose: 24 capsules of FMT at 3 months. |
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| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of treatment in halting the progression of decompensated cirrhosis. | Assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, HE). | Screening to month 12. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to transplant-free survival | Assessed by transplant-free survival | At month 1, month 3, month 6 and month 12 |
| Mortality rates | Assessed by mortality rates |
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Inclusion Criteria:
Exclusion Criteria:
Previous history of gastrointestinal surgery or colorectal cancer.
Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
Active Clostridium Difficile infection.
Patients on treatment with non-selective beta-blockers for <3 month or without stable doses.
Patients on treatment with any immunosuppressive drugs.
Patients on antiviral therapy for HCV or those who have received it within the last 12 months.
Patients on antiviral therapy for HBV therapy for < 12 months.
Patients with hepatocellular carcinoma, except for patients with early HCC (BCLC-0 or BCLC-A) or patients with previous history of HCC and absence of recurrence 2 years after treatment.
Patients admitted to the hospital for acute decompensation of the disease. These patients could be included after discharged as long as they do not present any of the following events:
Patients with ACLF according to the criteria published by Moreau et al. (Appendix 1).
Severe alcoholic hepatitis requiring corticosteroid therapy (MELD > 20) in the last 6 months.
Patients with active alcohol consumption of more than 21 units per week.
HIV infection.
Patients with a history of significant extra hepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD >2, chronic kidney disease with serum creatinine >2mg/dL or under renal replacement therapy.
Patients with current extra hepatic malignancies including solid tumours and hematologic disorders.
Patients with previous organ transplantation.
Pregnancy or breastfeeding.
Patients included in other clinical trials in the month before inclusion.
Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
Refusal to give informed consent.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eva Bonfill | Contact | +34932275400 | 4198 | BONFILL@recerca.clinic.cat |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| FMT Placebo | Other | Two doses: First dose: 24 capsules of FMT placebo at baseline. Second dose: 24 capsules of FMT placebo at 3 months. |
|
| At month 1, month 3, month 6 and month 12 |
| Rate of patients developing/ worsening individual complications of cirrhosis. | Assessed by ascites, acute kidney injury, bacterial infections, gastrointestinal bleeding and hepatic encephalopathy. | At baseline, month 1, month 3, month 6 and month 12. |
| Frequency of hospital admissions due to complications of cirrhosis. | Assessed by hospital admissions due to complications of cirrhosis. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Development of acute-on-chronic liver failure (ACLF) | Assessed by time to first episode of ACLF | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Development of acute-on-chronic liver failure (ACLF) | Assessed by total number of patients developing ACLF | At month 3, month 6 and month 12. |
| Development of acute-on-chronic liver failure (ACLF) | Assessed by severity of ACLF episodes based on ACLF grade (from grade 1 to grade 3) and CLIF-C-ACLF score | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Development of acute-on-chronic liver failure (ACLF) | Assessed by number and type of organ failures | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in systemic inflammatory response. | Evaluated by measurement in a large array of plasma cytokine levels including, but not limited to TNFα, IL-6, IL8, IL-10, IL-1β, IFN-ɣ, G-CSF, VCAM, VEGF, as well as an oxidized form of albumin, human nonmercaptalbumin-2 (HNA2). | At baseline, 1 month, 3 months, 6 months and 12 months. |
| PBMCs phenotype and function. | Analysed by flow cytometry, functional analysis, and RNAseq single cell analysis. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in different plasma and urine prognostic biomarkers. | Measurated by different plasma and urine prognostic biomarkers including, but not only, copeptin, NGAL, PD-L1, L-FABP. | At baseline, 1 month, 3 months, 6 months, and 12 months. |
| Changes from baseline in systemic hemodynamics and vasoactive hormones. | Measurated by systemic hemodynamics and vasoactive hormones: plasma renin concentration and plasma copeptin. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in blood levels of bacterial DNA or bacterial products. | Measurated by blood levels of bacterial DNA or bacterial products. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in liver function. | Evaluated by MELD (Model for End-stage Liver Disease) score. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in liver function. | Evaluated by CLIF-AD score. | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Changes from baseline in liver function. | Evaluated by Child Pugh Score.(from 1 point to 15 points) | At baseline, 1 month, 3 months, 6 months and 12 months. |
| Analyze microbiome composition from saliva and stool. | Measurated by analysis of microbial genes. | At baseline, and months 1, 3 and 6. |
| Changes in hepatic venous pressure gradient (HVPG) from baseline. | Measurated by the hepatic venous pressure gradient. | At baseline and month 6. |
| Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy. | Evaluated with data obtained from CLDQ (Chronic Liver Disease Questionnaire) questionnaire. | At baseline, 3 months, 6 months and 12 months. |
| Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy. | Evaluated with data obtained from Liver Frailty Index. | At baseline, 3 months, 6 months and 12 months. |
| Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy. | Evaluated with data obtained from PHES (Psychometric Hepatic Encephalopathy Score) questionnaire. | At baseline, 3 months, 6 months and 12 months. |
| Changes from baseline in AUDIT test. | Evaluated from AUDIT test | AUDIT test at baseline, 3 months, 6 months and 12 months |
| Changes from baseline in alcohol consumption. | Evaluated from PETh measurament. | PETh measurament test at baseline, 1 month, 3 months, 6 months and 12 months. |
| Assess the effect of FMT in ECG (Electrocardiogram). | Evaluated by changes in ACE score. | At screening, baseline and months 3,6 and 12. |
| Proportion of patients with treatment-related adverse events. | Evaluated by treatment-related adverse events. | Screening to month 12. |
| Proportion of patients with severe treatment-related adverse events. | Evaluated by treatment-related adverse events. | Screening to month 12. |