ALLOGENEIC FAECAL MICROBIOTA, POOLED for Decompensated cirrhosis

Stratification factors

• Child-Pugh class (B vs C)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old."}
• {"criterion_text":"- Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. Cirrhosis of any etiology may be included except from patients with cirrhosis due to autoimmune hepatitis, and patients with cirrhosis due to cholestatic liver disease can only be included in the study if they present clinical decompensation of cirrhosis (i.e. ascites)."}
• {"criterion_text":"- Child-Pugh B or C patients (7- up to 12 points)."}
• {"criterion_text":"- Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence (only if refraining from heterosexual intercourse during the period of twelve months of duration of the study). Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function."}

Exclusion criteria

• {"criterion_text":"- Previous history of gastrointestinal surgery or colorectal cancer."}
• {"criterion_text":"- Patients with previous history of intestinal obstruction or those who are at increased risk of this complication."}
• {"criterion_text":"- Active Clostridium Difficile infection."}
• {"criterion_text":"- Patients on treatment with non-selective beta-blockers for <3 month or without stable doses."}
• {"criterion_text":"- Patients on treatment with any immunosuppressive drugs."}
• {"criterion_text":"- Patients on antiviral therapy for HCV or those who have received it within the last 12 months."}
• {"criterion_text":"- Patients on antiviral therapy for HBV therapy for < 12 months."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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: a.\tBacterial infection within 10 days before study inclusion. b.\tGastrointestinal bleeding within 10 days before study inclusion. c.\tCurrent overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification."}
• {"criterion_text":"- Patients with ACLF according to the criteria published by Moreau et al."}
• {"criterion_text":"- Severe alcoholic hepatitis requiring corticosteroid therapy (MELD > 20) in the last 6 months."}
• {"criterion_text":"- Patients with active alcohol consumption of more than 21 units per week."}
• {"criterion_text":"- HIV infection."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with current extra hepatic malignancies including solid tumors and hematologic disorders."}
• {"criterion_text":"- Patients with previous organ transplantation."}
• {"criterion_text":"- Pregnancy or breastfeeding."}
• {"criterion_text":"- Patients included in other clinical trials in the month before inclusion."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Refusal to give informed consent."}

Primary endpoints

• {"endpoint_text":"- Efficacy of treatment in halting the progression of decompensated cirrhosis as assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, Hepatic Encephalopathy (HE)) during the study period.","definition_or_measurement_approach":"Assessed by time to first decompensation event during the study period (events include AKI, ascites, bacterial infection, gastrointestinal bleeding, Hepatic Encephalopathy (HE))."}

Secondary endpoints

• {"endpoint_text":"- Time to transplant-free survival and mortality rates at month 1, month 3, month 6 and month 12.","definition_or_measurement_approach":"Time-to-event analysis for transplant-free survival; mortality rates measured at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Development/worsening of individual complications of cirrhosis (ascites, AKI, bacterial infections, gastrointestinal bleeding, HE) assessed at baseline, month 1, month 3, month 6 and month 12.","definition_or_measurement_approach":"Assessment of individual complications at baseline and at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months and 12 months.","definition_or_measurement_approach":"Count of hospital admissions for cirrhosis complications at specified timepoints."}
• {"endpoint_text":"- Development of acute-on-chronic liver failure (ACLF) defined according to criteria by Moreau R, et al. (Time to first episode of ACLF; Total number of patients developing ACLF at month 3, month 6 and month 12; Severity of ACLF episodes based on ACLF grade and CLIF-C-ACLF score; Number and type of organ failures).","definition_or_measurement_approach":"Time to first ACLF episode; number of patients developing ACLF at months 3, 6 and 12; severity graded by ACLF grade and CLIF-C-ACLF score; number/type of organ failures."}
• {"endpoint_text":"- 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 1 month, 3 months, 6 months and 12 months. PBMCs phenotype and function will be analysed by flow cytometry, functional analysis, and RNAseq single cell analysis at baseline, 1 month, 3 months, 6 months and 12 mo.","definition_or_measurement_approach":"Panel of plasma cytokine measurements and HNA2 at months 1, 3, 6, 12; PBMC phenotype/function assessed by flow cytometry, functional assays and single-cell RNAseq at baseline, 1, 3, 6 and 12 months."}
• {"endpoint_text":"- Changes from baseline in different plasma and urine prognostic biomarkers including, but not only, copeptin, NGAL, PD-L1, L-FABP, at 1 month, 3 months, 6 months, and 12 months.","definition_or_measurement_approach":"Measurement of specified plasma and urine biomarkers at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma renin concentration and plasma copeptin at 1 month, 3 months, 6 months and 12 months.","definition_or_measurement_approach":"Plasma renin concentration and copeptin measured at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Changes from baseline in blood levels of bacterial DNA or bacterial products at 1 month, 3 months, 6 months and 12 months.","definition_or_measurement_approach":"Measurement of bacterial DNA/products in blood at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Changes from baseline in liver function, evaluated by MELD score, CLIF-AD score and Child Pugh Score at 1 month, 3 months, 6 months and 12 months.","definition_or_measurement_approach":"MELD, CLIF-AD and Child-Pugh scores evaluated at months 1, 3, 6 and 12."}
• {"endpoint_text":"- Analyze microbiome composition from saliva and stool by analysis of microbial genes at baseline, and months 1, 3 and 6.","definition_or_measurement_approach":"Microbial gene analysis from saliva and stool at baseline, months 1, 3 and 6."}
• {"endpoint_text":"- Changes in HVPG from baseline to month 6.","definition_or_measurement_approach":"Hepatic venous pressure gradient measured at baseline and month 6."}
• {"endpoint_text":"- The data obtained from CLDQ (Chronic Liver Disease Questionnaire), Liver Frailty Index and PHES (Psychometric Hepatic Encephalopathy Score) questionnaires to assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy at baseline, 3 months, 6 months and 12 months.","definition_or_measurement_approach":"Questionnaire-based assessments (CLDQ, Liver Frailty Index, PHES) at baseline, 3, 6 and 12 months."}
• {"endpoint_text":"- Changes from baseline in AUDIT test at 3 months, 6 months and 12 months. Alcohol consumption will be monitorized by PETh measurement.","definition_or_measurement_approach":"AUDIT scores at months 3, 6 and 12; PETh measurement to monitor alcohol consumption."}
• {"endpoint_text":"- Changes in ACE score to assess the effect of FMT in ECG at screening, baseline and months 3, 6 and 12.","definition_or_measurement_approach":"ACE score from ECG at screening, baseline and months 3, 6 and 12."}
• {"endpoint_text":"- Proportion of patients and severity of treatment-related adverse events during the study period.","definition_or_measurement_approach":"Recording and classification of treatment-related adverse events and their severity during study period."}

Spain

Earliest CTIS Part Ii Submission Date

04-12-2024

Latest Decision Or Authorization Date

30-04-2025

Processing Time Days

147

Number Of Sites

8

Number Of Participants

190

Primary sponsor

Full Name

Consorcio Centro De Investigacion Biomedica En Red

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain