Clinical trial NCT06533852: Fecal Microbiome Transplantation in Cirrhosis: Trial in Patients With Decompensated Cirrhosis
Official title: Fecal Microbiome Transplantation in Cirrhosis: Randomized, Double-blinded, Placebo-Controlled Trial in Patients With Decompensated Cirrhosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Decompensated Cirrhosis
Lead sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
Sponsor class: OTHER_GOV
First posted: 2024-08-01
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old.
2. 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).
3. Child-Pugh B or C patients (7- up to 12 points).
4. 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). Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.

Exclusion Criteria:

1. Previous history of gastrointestinal surgery or colorectal cancer.
2. Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
3. Active Clostridium Difficile infection.
4. Patients on treatment with non-selective beta-blockers for \<3 month or without stable doses.
5. Patients on treatment with any immunosuppressive drugs.
6. Patients on antiviral therapy for HCV or those who have received it within the last 12 months.
7. Patients on antiviral therapy for HBV therapy for \< 12 months.
8. 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.
9. 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:

   1. Bacterial infection within 10 days before study inclusion.
   2. Gastrointestinal bleeding within 10 days before study inclusion.
   3. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
10. Patients with ACLF according to the criteria published by Moreau et al. (Appendix 1).
11. Severe alcoholic hepatitis requiring corticosteroid therapy (MELD \> 20) in the last 6 months.
12. Patients with active alcohol consumption of more than 21 units per week.
13. HIV infection.
14. 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.
15. Patients with current extra hepatic malignancies including solid tumours and hematologic disorders.
16. Patients with previous organ transplantation.
17. Pregnancy or breastfeeding.
18. Patients included in other clinical trials in the month before inclusion.
19. 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.
20. Refusal to give informed consent.

Primary outcomes:
measure: Efficacy of treatment in halting the progression of decompensated cirrhosis.
timeFrame: Screening to month 12.
Secondary outcomes:
measure: Time to transplant-free survival
timeFrame: At month 1, month 3, month 6 and month 12
measure: Mortality rates
timeFrame: At month 1, month 3, month 6 and month 12
measure: Rate of patients developing/ worsening individual complications of cirrhosis.
timeFrame: At baseline, month 1, month 3, month 6 and month 12.
measure: Frequency of hospital admissions due to complications of cirrhosis.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Development of acute-on-chronic liver failure (ACLF)
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Development of acute-on-chronic liver failure (ACLF)
timeFrame: At month 3, month 6 and month 12.
measure: Development of acute-on-chronic liver failure (ACLF)
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Development of acute-on-chronic liver failure (ACLF)
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in systemic inflammatory response.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: PBMCs phenotype and function.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in different plasma and urine prognostic biomarkers.
timeFrame: At baseline, 1 month, 3 months, 6 months, and 12 months.
measure: Changes from baseline in systemic hemodynamics and vasoactive hormones.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in blood levels of bacterial DNA or bacterial products.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in liver function.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in liver function.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Changes from baseline in liver function.
timeFrame: At baseline, 1 month, 3 months, 6 months and 12 months.
measure: Analyze microbiome composition from saliva and stool.
timeFrame: At baseline, and months 1, 3 and 6.
measure: Changes in hepatic venous pressure gradient (HVPG) from baseline.
timeFrame: At baseline and month 6.
measure: Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy.
timeFrame: At baseline, 3 months, 6 months and 12 months.
measure: Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy.
timeFrame: At baseline, 3 months, 6 months and 12 months.
measure: Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy.
timeFrame: At baseline, 3 months, 6 months and 12 months.
measure: Changes from baseline in AUDIT test.
timeFrame: AUDIT test at baseline, 3 months, 6 months and 12 months
measure: Changes from baseline in alcohol consumption.
timeFrame: PETh measurament test at baseline, 1 month, 3 months, 6 months and 12 months.
measure: Assess the effect of FMT in ECG (Electrocardiogram).
timeFrame: At screening, baseline and months 3,6 and 12.
measure: Proportion of patients with treatment-related adverse events.
timeFrame: Screening to month 12.
measure: Proportion of patients with severe treatment-related adverse events.
timeFrame: Screening to month 12.
Other outcomes:
Locations:
Study officials:
References: