Evaluation of the Survival Benefit of the Adjunction of Pentoxifylline to Corticosteroids in Patients Suffering From Severe Alcoholic Hepatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 278
- 试验地点
- 15
- 主要终点
- Overall Survival
研究概览
简要总结
The treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge for clinicians involved in the management of severe alcoholic liver disease. In patients with Maddrey function higher than 32, compelling evidence from data has shown that corticosteroids improve short-term survival. However, novel strategies or molecules are required in light of the fact that approximately 40 % of patients continue to die at 6 months. A double-blinded randomized controlled trial of 101 patients has showed that Pentoxifylline improves survival of patients with severe AH, as compared to placebo. In terms of mechanisms, the effect of pentoxifylline is related to prevention of hepatorenal function whereas corticosteroids induce an early improvement in liver function. When considering these differences of mechanisms, many clinicians suggest that the addition of pentoxyfilline to corticosteroids is an attractive option that needs to be tested in patients with severe AH.
详细描述
The aim of the present study is to determine whether or not the adjunction of Pentoxifylline to corticosteroids would improve 6-month survival of patients with severe alcoholic hepatitis. This multicenter, randomized, double-blinded, controlled, phase 3 trial was conducted in 24 centers located in France and Belgium. Alcoholic hepatitis was biopsy-proven. All eligible patients were randomly assigned in a 1:1 ratio to receive corticosteroids + Pentoxifylline or corticosteroids + Placebo. The primary outcome of the study was 6-month survival. Assuming a two-sided type I error of 0.05, a randomization ratio of 1:1 between the 2 groups, 6-month survival of 64% in the Placebo and Corticosteroids group and of 78 % in the Pentoxifylline and Corticosteroids group, we estimated that with 268 randomized patients (134 in each group), the study would have a power of 80% to detect this increase in 6-month survival in the Pentoxifylline and Corticosteroid group.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Alcohol consumption more than 40 gram/day for women and 50 gram/day for men
- •Maddrey discriminant function higher than 32
- •Onset of jaundice within the 3 previous months
- •Biopsy-proven alcoholic hepatitis
排除标准
- •Hypersensitivity to pentoxifylline
- •Any severe disease that may potential affect survival such as cardiac failure, ischemic cardiopathy, respiratory failure
- •Any neoplasm that occurred within the 2 previous years
- •Hepatocellular carcinoma or any previous diagnosis of hepatocellular carcinoma
- •Portal thrombosis
- •Severe gastrointestinal bleeding
- •Uncontrolled sepsis within the 7 previous days
- •Hepatorenal syndrome type I
- •Viral and fungal infection
- •Acute pancreatitis
- •Any tuberculosis that occurred within the 5 previous years
- •Psychiatric disorders that contraindicate the use of corticosteroids
- •Infection related to virus of the hepatites B or C
- •HIV infection (Human immunodeficiency virus)
- •Any treatment with corticosteroids, immunosuppressive agents, budesonide, thalidomide or pentoxifylline that was given within the previous year
- •Pregnancy or breast feeding
研究组 & 干预措施
Pentoxifylline + Prednisolone
Pentoxifylline 400 mg prolonged-released tablets 3 time a day [1200 mg/day]
- Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]
干预措施: placebo (Drug)
Placebo + Prednisolone
Placebo prolonged-release tabled 3 time a day
- Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]
干预措施: Pentoxifylline (Drug)
结局指标
主要结局
Overall Survival
时间窗: 6 months
次要结局
- Hepatorenal syndrome(6 months)
- Score of Lille model(Seven days)
- Percentage of Meld score (Model for End-stage Liver Disease) higher than 17(6 months)