Corticosteroids in Severe Alcoholic Hepatitis Patients With Early Spontaneous Improvement
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Mortality at 90 days
研究概览
简要总结
Approximately 50% of patients admitted for severe AH will have spontaneous improvement of liver function before initiation of therapy (ie decrease in mDF between hospital admission and initiation of steroids). These patients have a better prognosis than patients without spontaneous improvement of liver function. It has never been demonstrated that corticosteroids improve survival in severe AH patients with spontaneous improvement of liver function. Our hypothesis is that severe AH patients with spontaneous improvement of liver function represent a group who could most benefit from steroids
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blind randomized trial Investigator, patients, and care providers will be masking Only statisticians and pharmacist will not be masking
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical syndrome of alcoholic hepatitis:
- •recent jaudice or in recent aggravation (< 3 months) serum bilirubin > 5 mg/dL history of excess alcohol abuse (> 40g/day)
- •Alcoholic hepatitis proven by a liver biopsy (histological criteria of alcoholic hepatitis defined according to EASL clinical practice guidelines : steatosis, hepatocyte ballooning, and an inflammatory infiltrate with PMNs). The results of the liver biopsy are not mandatory for inclusion. However, the biopsy must be planned at the latest on day
- •When the results become available and do not confirm alcoholic hepatitis, the patient must discontinue the study.
- •Spontaneous liver function improvement, defined by a decrease in serum bilirubin level > 10% between admission and day 5-10 after admission
- •less than 2 weeks since admission to hospital
- •Maddrey discriminant function* greater than or equal to 32
- •Subjects must voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures.
- •Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements.
- •Patients with significant hepatic encephalopathy are not excluded from participation to the trial. In this case, the patient should be accompanied by a legal representative that will decide participation in the clinical study and sign ICF.
排除标准
- •Other causes of liver disease including viral hepatitis (positive HBs antigen, HCV RNA positive), auto-immune hepatitis, biliary obstruction
- •Other disease compromising 90-day survival
- •Positive HIV serology
- •Uncontrolled infection All patients will be screened for infection. This will involve chest radiography, urinalysis, PMNs count in ascites (if ascites present). All other sign or clinical suspicion of infection with or without antibiotherapy will be recorded as an infection.
- •Positive culture and initiation of antibiotics with clinical or radiological signs of infection, as well as clinical suspicion, will be recorded as infection.
- •Patients with evidence of sepsis will be treated for a minimum of 2 days with appropriate antibiotics. Once the local principal investigator considers that the sepsis is under control, the patient may be rescreened and randomised.
- •Uncontrolled gastrointestinal bleeding Bleeding must be judged as controlled for at least 5 days
- •Patient with serum creatinine > 2.5 mg/dL, under renal replacement therapy or under terlipressine (or other vasoactive drugs)
- •Pentoxyphilline therapy
- •Pregnant or lactating women
研究组 & 干预措施
methylprednisolone
Patients will receive 28 days of methylprednisolone 32 mg/day
干预措施: Methylprednisolone or placebo (Drug)
placebo
Patients will receive 28 days of matching placebo
干预措施: Methylprednisolone or placebo (Drug)
结局指标
主要结局
Mortality at 90 days
时间窗: 90 days
To determine whether Methylprednisolone compared to placebo improve the 90 day mortality from patients with severe AH and spontaneous improvement of liver function
次要结局
- Mortality at 28 days(28 days)
- Incidence of infections during the study period (90 days)(90 days)