Molecular Adsorbent Recirculating System (MARS®) for the Treatment of Patients With Hypoxic Hepatitis - a Prospective Randomized Controlled Clinical Study
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- difference of the indocyanine plasma disappearance rate (ICG-PDR)
研究概览
简要总结
Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Early therapeutic intervention is of central prognostic importance in patients with HH to improve the hemodynamic impairment as early as possible, to reduce hyperammonemia and hepatic encephalopathy, to avoid progression of organ failure and to improve outcome. Studies reported that Molecular Adsorbent Recirculating System (MARS®) therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. The study hypothesis is that MARS® therapy in critically ill patients with severe HH improves hepatic hemodynamics and function and consecutively the course of the disease. 40 patients with suffering of severe HH with aminotransferase levels > 40 times the upper limit of normal of more than 12 hours will be randomized 1:1 to MARS® therapy (n=20) or conventional therapy (n=20). 4 MARS®-sessions will be performed on three consecutive days, each for at least 12 hours. Treatment will be continued under special circumstances. The maximum duration of the treatment phase is 7 days. The primary endpoint is the difference of the indocyanine plasma disappearance rate at day 7. The expected duration of the study is 2 years.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •presence of severe hypoxic hepatitis with aminotransferase levels > 40 times the upper limit of normal
- •duration of hypoxic hepatitis more than 12 hours
- •age >/= 18 years
排除标准
- •age < 18 years
- •pregnancy
- •DNR - order
- •liver cirrhosis
- •Cardiopulmonary resuscitation with unknown neurological outcome and/or hypoxic brain damage
- •Expected survival of less than 24 hours
研究组 & 干预措施
Control
Patients with severe HH will be treated with standard medical therapy (i.e. vasopressor support with norepinephrine in refractory hypotension = RR mean < 65 mmHg, positive inotropic support with dobutamine if the central venous oxygen saturation < 70%, renal replacement therapy in case of severe metabolic acidosis and/or renal failure, antibiotic treatment in case of suspected or proven infection, mechanical ventilation in case of severe hypoxemia or hypercapnia and/or GCS <= 8.
MARS-Group
20 patients will be allocated by randomization to the MARS arm. Additionally to standard medical therapy they will receive 4 MARS sessions on three consecutive days, MARS® therapy will be applied for at least 12 hours per session. Thereafter, MARS® treatment will be continued if the patient still has increasing aminotransferase levels, requires vasopressor support or suffers from cholestasis (defined as serum bilirubin levels > 5 mg/dL) for 3 sessions again. There will be a maximum of 7 MARS ® sessions per patient.
干预措施: MARS (Device)
结局指标
主要结局
difference of the indocyanine plasma disappearance rate (ICG-PDR)
时间窗: Days 1-7
The primary endpoint will be the difference of the indocyanine plasma disappearance rate (ICG-PDR) at day 7. Only in case of major differences in baseline values of ICG-PDR we will use the change from baseline to day 7 of ICG-PDR (delta ICG-PDR) as outcome. Assuming normal distribution of ICG-PDR, we will formally test the null-hypothesis of no difference between intervention group and control using an independent sample t-test. The assumption of a normal distribution will be founded on visually inspecting a histogram and using the Shapiro Wilks test for normal distribution. If the assumption of normality does not hold data will be compared using the Mann-Whitney U-test. A p-level of \< 0.05 will be considered statistically significant. Furthermore a linear random coefficient model will be used to incorporate daily measurements of ICG-PDR during the course of the study in terms of a repeated measures design.
次要结局
- hospital - length of stay(1-90)
- 28 day mortality(28 days)
- number of organ failure on day 7(7 days)
- duration of vasopressor support(1-28)
- ICU - length of stay(1-28)
- 7-day mortality(7 days)
- number of organ failure on day 28(28 days)
- markers of liver function(1-28)
- systemic hemodynamics(7 days)
- number of complications of HH(1-28)
- biomarkers(0-28)
- duration of mechanical ventilation(1-28)
- duration of renal replacement therapy(1-28)
- number of vasopressor free days(28 days)
- necessity of renal replacement therapy(1-28)
- 90 days mortality(90 days)
研究者
Valentin Fuhrmann
Associate Professor
Medical University of Vienna