Fecal Microbiota Therapy in Steroid Ineligible Alcoholic Hepatitis: A Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Mortality at 3 months
研究概览
简要总结
Alcoholic hepatitis, the most florid form of alcoholic liver disease, has a very high short-term mortality of up to 50% and no specific therapies are available other than steroids. Steroids also only show a limited utility in improving the short-term survival and boast no evidence of any long-term benefits. Additionally, only a small proportion of patients with alcoholic hepatitis are eligible to receive steroids. Thus, a large number of patients are either not eligible or do not respond to steroids and this group outnumbers those who do respond to steroids, leaving us without any specific therapeutic options for a majority of these individuals.Even liver transplantation is not feasible in most cases due to the presence of sepsis or recent alcohol consumption and many ethical and logistic issues are involved despite the documented safety and survival benefits of early liver transplantation in patients with severe alcoholic hepatitis (SAH) not responding to medical management.Therefore, newer, more effective, and nontransplant therapeutic options for managing severe alcoholic hepatitis are needed. Since gut dysbiosis, leaky gut, and products of the gut microbiome reaching the liver are the main culprits in the development of alcoholic hepatitis, targeting qualitative and quantitative changes in the gut microbiome remains an important strategy in developing new therapies for alcoholic hepatitis. Among others, the modulation of gut microbiota by fecal microbiota transplantation (FMT) has recently been conceptualized and evaluated as a potential therapeutic strategy in both preclinical and clinical studies.
详细描述
AIM- To assess survival benefit at 3 month, in patients of severe alcoholic hepatitis who are steroid ineligible.
Methodology:
Study population: Fecal microbiota therapy in steroid ineligible Alcoholic hepatitis: Randomized controlled trial.
Study design:
A prospective, randomized controlled trial. The study will be conducted on the consecutive patients presenting with severe Alcoholic hepatitis to the wards of Department of Hepatology, ILBS, New Delhi from feb 2022 to February 2023 who meet the inclusion criteria.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Steroid ineligible severe alcoholic hepatitis as per definition
- •Informed consent
- •Age 18 - 70 years
- •Liver biopsy -if Feasible
- •Model for End-Stage Liver Disease (MELD) ≥ 20 and Maddrey DF ≥ 32
排除标准
- •UGI Bleed within last one month
- •More then 3 organ failure requiring support
- •Mechanically ventilated patient , (patients requiring ICU/ HDU care) (On inotropic support)
- •Uncontrolled sepsis, DIC
- •Gut paralysis
- •Active hepatic or extra hepatic malignancy
- •Renal failure creatinine > 2.5
- •Prior SBP/active SBP
- •Intestinal conditions like IBD, SIBO
- •Donor evaluation The subjects will be screened for
- •Routine laboratory tests (CBC; LFT; KFT; PT; INR)
- •Fasting blood sugar
- •Lipid profile
- •Stool routine and microscopy stool ova & cysts.
- •Stool culture
- •Clostridium difficile toxin
- •Helicobacter pylori stool antigen
- •Cryptosporidium & Isospora (acid fast stain) Exclusion criteria for Donor
- •Antibiotic usage within 3 months of enrollment
- •Gastroenteritis within last 2 months
- •Diabetes mellitus
- •Inflammatory bowel disease
- •Any Malignancy
- •Chronic Kidney disease, Coronary artery disease
- •Cerebrovascular accident or chronic obstructive pulmonary disease
- •HBsAg, Anti HCV, HIV seropositivity
- •Transaminitis, dyslipidemia
- •Ova or cyst in stool, C. difficile toxin Positive
- •Chronic alcohol intake
- •Active substance abuse
研究组 & 干预措施
Fecal Transplantation
- Donors will be supplied clean, sealable containers for collection and transport of stool. Containers will be labeled with the name, UHID and date/time of stool collection.
- Collected stool will be immediately transferred to the laboratory facility for processing and used within 6 hours collection
- Stool sample from Healthy donor will be processed
- Patient preparation
- Patient was kept NPO for 4 hours prior to stool instillation
- Iv antibiotics were continued as per treating doctor in the event of sepsis
- The patient was allowed to consume the prescribed diet 2 hours after the procedure instillation
- Methods of FMT infusion.
- Seven doses (30gm one dose) of FMT will be given via jejunal port of NJ/NG tube
干预措施: Fecal Transplantation (Other)
Standard Medical Treatment
Standard Medical Treatment
干预措施: Standard Medical Treatment (Drug)
结局指标
主要结局
Mortality at 3 months
时间窗: 3 months
Liver transplant free survival
时间窗: 3 months
次要结局
- End of study period(6 months)
- Mortality(1 month)
- Post therapy assessment in the form of clinical improvement (hepatic encephalopathy, ascites , improvement in jaundice)(both ascites and HE if present)(6 months)
- Frequency of decompensation events on follow up period(6 months)
