NCT06533852招募中3 期
Fecal Microbiome Transplantation in Cirrhosis: Randomized, Double-blinded, Placebo-Controlled Trial in Patients With Decompensated Cirrhosis
Consorcio Centro de Investigación Biomédica en Red (CIBER)14 个研究点 分布在 1 个国家目标入组 190 人开始时间: 2025年7月16日最近更新:
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 190
- 试验地点
- 14
- 主要终点
- Efficacy of treatment in halting the progression of decompensated cirrhosis.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old.
- •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).
- •Child-Pugh B or C patients (7- up to 12 points).
- •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.
排除标准
- •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:
- •Bacterial infection within 10 days before study inclusion.
- •Gastrointestinal bleeding within 10 days before study inclusion.
- •Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
- •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.
结局指标
主要结局
Efficacy of treatment in halting the progression of decompensated cirrhosis.
时间窗: Screening to month 12.
Assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, HE).
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.
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.
次要结局
- Time to transplant-free survival(At month 1, month 3, month 6 and month 12)
- Mortality rates(At month 1, month 3, month 6 and month 12)
- Rate of patients developing/ worsening individual complications of cirrhosis.(At baseline, month 1, month 3, month 6 and month 12.)
- Frequency of 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)(At baseline, 1 month, 3 months, 6 months and 12 months.)
- Development of acute-on-chronic liver failure (ACLF)(At month 3, month 6 and month 12.)
- Changes from baseline in systemic inflammatory response.(At baseline, 1 month, 3 months, 6 months and 12 months.)
- PBMCs phenotype and function.(At baseline, 1 month, 3 months, 6 months and 12 months.)
- Changes from baseline in different plasma and urine prognostic biomarkers.(At baseline, 1 month, 3 months, 6 months, and 12 months.)
- Changes from baseline in systemic hemodynamics and vasoactive hormones.(At baseline, 1 month, 3 months, 6 months and 12 months.)
- Changes from baseline in 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.(At baseline, 1 month, 3 months, 6 months and 12 months.)
- Analyze microbiome composition from saliva and stool.(At baseline, and months 1, 3 and 6.)
- Changes in hepatic venous pressure gradient (HVPG) from baseline.(At baseline and month 6.)
- Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy.(At baseline, 3 months, 6 months and 12 months.)
- Changes from baseline in AUDIT test.(AUDIT test at baseline, 3 months, 6 months and 12 months)
- Changes from baseline in alcohol consumption.(PETh measurament test at baseline, 1 month, 3 months, 6 months and 12 months.)
- Assess the effect of FMT in ECG (Electrocardiogram).(At screening, baseline and months 3,6 and 12.)
- Proportion of patients with treatment-related adverse events.(Screening to month 12.)
- Proportion of patients with severe treatment-related adverse events.(Screening to month 12.)
- Time to transplant-free survival and mortality rates at month 1, month 3, month 6 and month 12.
- 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.
- Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months and 12 months.
- 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).
- 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.
- 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.
- 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.
- Changes from baseline in blood levels of bacterial DNA or bacterial products at 1 month, 3 months, 6 months and 12 months.
- 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.
- Analyze microbiome composition from saliva and stool by analysis of microbial genes at baseline, and months 1, 3 and 6.
- Changes in HVPG from baseline to month 6.
- 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.
- Changes from baseline in AUDIT test at 3 months, 6 months and 12 months. Alcohol consumption will be monitorized by PETh measurement.
- Changes in ACE score to assess the effect of FMT in ECG at screening, baseline and months 3, 6 and 12.
- Proportion of patients and severity of treatment-related adverse events during the study period.
研究者
Pere Ginès
Scientific
Consorcio Centro De Investigacion Biomedica En Red
研究点 (14)
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