Fecal Microbiome Transplantation in Cirrhosis: Trial in Patients With Decompensated Cirrhosis

Официальное название

Fecal Microbiome Transplantation in Cirrhosis: Randomized, Double-blinded, Placebo-Controlled Trial in Patients With Decompensated Cirrhosis

Обзор

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.

Вмешательства

• Препарат Fecal Microbiome Transplantation (FMT)
  Two doses: First dose: 24 capsules of FMT at baseline. Second dose: 24 capsules of FMT at 3 months.
• Другое FMT Placebo
  Two doses: First dose: 24 capsules of FMT placebo at baseline. Second dose: 24 capsules of FMT placebo at 3 months.

Первичные конечные точки

• Efficacy of treatment in halting the progression of decompensated cirrhosis. [Срок оценки: Screening to month 12.]

Вторичные конечные точки (12)

• Time to transplant-free survival [Срок оценки: At month 1, month 3, month 6 and month 12]
• Mortality rates [Срок оценки: At month 1, month 3, month 6 and month 12]
• Rate of patients developing/ worsening individual complications of cirrhosis. [Срок оценки: At baseline, month 1, month 3, month 6 and month 12.]
• Frequency of hospital admissions due to complications of cirrhosis. [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• Development of acute-on-chronic liver failure (ACLF) [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• Development of acute-on-chronic liver failure (ACLF) [Срок оценки: At month 3, month 6 and month 12.]
• Development of acute-on-chronic liver failure (ACLF) [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• Development of acute-on-chronic liver failure (ACLF) [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• Changes from baseline in systemic inflammatory response. [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• PBMCs phenotype and function. [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]
• Changes from baseline in different plasma and urine prognostic biomarkers. [Срок оценки: At baseline, 1 month, 3 months, 6 months, and 12 months.]
• Changes from baseline in systemic hemodynamics and vasoactive hormones. [Срок оценки: At baseline, 1 month, 3 months, 6 months and 12 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Испания · 8 центров

• Hospital Clínic de Barcelona — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitari Vall Hebron — Barcelona
• Hospital General Universitario Gregorio Marañón — Madrid
• Hospital General Universitario Puerta de Hierro — Madrid
• Hospital Universitario Ramón y Cajal — Madrid
• Corporació Sanitaria Universitaria Parc Taulí — Sabadell
• Hospital Universitario Marqués de Valdecilla — Santander

Идентификаторы

NCT: NCT06533852 · 2023-509151-13-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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