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临床试验/NCT04103840
NCT04103840Unknown不适用

Assessment of Invasive Fungal Infections as a Result of Fungal Dysbiosis in Patients With Severe Alcohol-associated Hepatitis

Post Graduate Institute of Medical Education and Research, Chandigarh1 个研究点 分布在 1 个国家目标入组 160 人开始时间: 2019年8月27日最近更新:
适应症

试验速览

阶段
不适用
发起方
入组人数
160
试验地点
1
主要终点
Survival

研究概览

简要总结

Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet little is known about the role of intestinal fungi, or mycobiota in liver disease. Although the intestinal microbiome contains bacteria, fungi, and viruses, research in the field of liver disease has almost exclusively focused on the interaction between the host and gut bacteria. The fungal microbiota is an integral part of the gastrointestinal micro-ecosystem with up to 106 microorganisms per gram of faeces. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi have been demonstrated in prior studies. Alcohol-dependent patients display a reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients also demonstrate systemic exposure and immune response to mycobiota. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease especially alcoholic hepatitis. In this study, we will attempt to find out the natural fungal mycobiome in Severe alcoholic hepatitis when compared with apparently healthy asymptomatic controls from their family. This will allow us to therapeutically modify the unbalanced gut microbiota and improve patient outcomes. Secondly, it will provide further insight as to why alcohol-associated hepatitis patients are particularly susceptible to fungal infections. In the age of frequent antibacterial drug therapy, the role of commensal and pathogenic fungi in the human gut has gained paramount importance.

详细描述

The patients of severe alcohol-associated hepatitis admitted under Department of Hepatology, in Liver intensive Care Unit (LICU) Male or Female medical wards or coming to follow up in Liver clinic of Postgraduate Institute of Medical Education and Research, Chandigarh, India from will be screened for enrolment after ethical approval from the institute ethics committee. Both previously compensated and decompensated patients will be enrolled in this prospective observational pilot study. All patients will be followed up at 30 and 90 days from inclusion into the study.

Estimation of sample size Sample size will be estimated based on previous studies. This is a pilot prospective observational study. Based on currently available data from our centre on acute-on chronic liver failure, 22.5% of cirrhotics have suspected IFI, and up to 25% of SAH have suspicion for IFI, it is estimated that a total sample size of 60 patients would be required, with an effect size of 0.5, alpha 0.05, and power 0.85. Therefore, 80 patients will be required to enroll to account for 15% attrition. Hence, we propose to enroll 80 consecutive patients with SAH with 80 matched controls from their family starting from 15th August 2019.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

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

入选标准

  • Severe Alcoholic Hepatitis
  • Aged between 18 Years to 70 Years
  • Either gender
  • Study will also include age matched healthy controls from the patient's family

排除标准

  • Inability to obtain informed consent from patient or relatives.
  • Severe cardiopulmonary disease
  • HIV infection
  • Recent abdominal surgery (with in last 6 months)
  • Patient on immunosuppressive drugs
  • Malignancies including Hepatocellular carcinoma
  • Gastrointestinal (GI bleed) in the last 4 weeks
  • Oral antibiotics or antifungals taken in last 2 weeks.

结局指标

主要结局

Survival

时间窗: at Day 28 and Day 90

Patients who survive till Day 28 and Day 90

次要结局

  • Clinical and biochemical parameters will be compared at 0 and 90 days(90 days)
  • Clinical events like decompensation in the form of new onset ascites, variceal bleed, renal dysfunction, hepatic encephalopathy, infections(90 days)
  • Non-elective hospital admissions(90 Days)

研究者

发起方
Post Graduate Institute of Medical Education and Research, Chandigarh
申办方类型
Other
责任方
Principal Investigator
主要研究者

Madhumita Premkumar

Assistant Professor, Department of Hepatology

Post Graduate Institute of Medical Education and Research, Chandigarh

研究点 (1)

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