Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 44
- 主要终点
- 60 day survival
研究概览
简要总结
This is a prospective, randomized, open-label, multicentre study involving European centers with experience in the management of PHLF to assess the impact of early liver support with MARS on survival in patients with post-hepatectomy liver failure (PHLF).
详细描述
PHLF is a major risk factor for mortality in patients who underwent major hepatectomy. A specific treatment is yet not available. In a primary proof-of-concept study, it was shown that it is safe and feasible to use MARS in patients with PHLF early after hepatectomy. Survival was superior to a historical control group.
This study will include patients with early, primary PHLF (based on the 50:50 criteria) after major liver surgery. Patients will be randomized 1:1 to receive standard treatment alone or standard treatment + liver dialysis using the Molecular Adsorbent Recirculating System (MARS). Relevant outcome along with several physiological parameters will be assessed.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients subjected for major liver surgery (4 or more Couinaud segments) or patients undergoing a 2nd, 3rd or 4th hepatic resection. Pre-operative chemotherapy and/or biological agents are allowed.
- •Primary PHLF occurring early after surgery defined by the 50:50 criteria (from PO day 5 to day 14) or by the presence of hepatic encephalopathy grade 2 or more and the 50:50 criteria (from PO day 3 to 4).
- •Written informed consent.
排除标准
- •ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) procedure.
- •In patients with chronic liver disease presence of significant portal hypertension (hepatic venous pressure gradient ≥ 10 mmHg and/or Fibroscan ≥ 21kPa) prior to surgical intervention.
- •Any contraindication for MARS therapy such as uncontrolled active bleeding, platelet counts <20.000 /µl or uncontrolled infection (presence of fever or adequate antibiotic therapy for less than 48h), septic shock, haemodynamic instability requiring inotropic support (noradrenaline > 1mg/h).
- •PHLF occurring after post operative day
- •Secondary PHLF: post-operative liver failure secondary to vascular (outflow or inflow thrombosis) or septic problems.
- •Persistant biliary complications (infected biloma, main biliary tree damage).
- •Inability or unwilling of the patient or family to give informed consent.
研究组 & 干预措施
Standard medical treatment + MARS
Patients assigned to the control arm will receive standard medical treatment (SMT) and liver dialysis using Molecular Adsorbent Recirculating System (MARS).
干预措施: Molecular Adsorbent Recirculating System (Device)
Standard medical treatment
Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol.
干预措施: Standard medical treatment (SMT) (Other)
结局指标
主要结局
60 day survival
时间窗: From randomization to death from any cause, assessed up to 60 days postop
Overall survival rate from time of randomization to death from any cause
次要结局
- 28 day survival(From randomization to death from any cause, assessed up to 28 days post-op)
- 6 month survival(From randomization to death from any cause, assessed up to 6 months postop)
- 1 year survival(From randomization to death from any cause, assessed up to 1 year.)
- 90 day survival(From randomization to death from any cause, assessed up to 90 days postop)
- Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)(From randomization up to 1 year.)
- Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)(From randomization up to 1 year.)
- Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on extra-hepatic function (SOFA scoring)(From randomization up to 1 year.)
- Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).(At randomization (day 0) and on days 5, 10 and 30 .)
- Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on liver performance status.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.(At randomization (day 0) and on days 5 and 10.)
- Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.(At randomization (day 0) and on day 10.)
- Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography.(At randomization (day 0) and on day 10.)
- Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.(At randomization (day 0) and on day 10.)
- Impact of MARS therapy on liver function(From randomization up to 1 year.)
研究者
Stefan Gilg, MD, PhD
Principal Investigator
Karolinska University Hospital