A Randomized Multicentre, Double-Blinded and Placebo-Controlled, Trial of Human Albumin in the Treatment of Decompensated Cirrhosis Guided by the MICROB-PREDICT Biomarker
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 240
- 试验地点
- 12
- 主要终点
- Cumulative number of liver-related clinical outcomes
研究概览
简要总结
The goal of this clinical biomarker validation trial is to test the effect of a predictive biomarker panel to human albumin infusions in patients with liver cirrhosis and ascites. The main questions it aims to answer are:
- If the predictive biomarker panel can identify patients who are likely to benefit from regular human albumin infusions
- If the predictive biomarker panel can lower the number-needed-to-treat of regular human albumin infusions in patients with liver cirrhosis and ascites
The predictive biomarker panel will stratify patients into either a high- or low-expected effect of human albumin infusions. Hereafter are participants randomized into treatment arms.
Participants in the active treatment arm will receive regular human albumin infusions during a course of 6 months. Infusions will occur every 10th day for the duration of the study.
Researchers will compare 20% human albumin infusions with regular 0.9% sodium chloride to identify the effects on the number of liver-related events.
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, Investigator, Outcomes Assessor)
盲法说明
There will exist two levels of masking in the current trial. Masking of biostratification outcome (high expected effect of human albumin or low expected effect of human albumin): Participant, Investigator and Outcome Assessor Masking of treatment assignment (human albumin 20% or saline 0.9%): Participant and Outcome Assessor
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
- •Decompensated liver cirrhosis defined as Child-Pugh score 7-12
- •Clinical and/or ultrasound evidenced ascites
- •Age ≥ 18 years
- •At least five days since resolution of a decompensation event or any condition requiring hospitalisation
排除标准
- •Patients with acute or subacute liver failure without underlying cirrhosis
- •Patients with cirrhosis who develop decompensation in the postoperative period following partial hepatectomy
- •Refractory ascites as defined by the International Ascites Club
- •Existing TIPS inserted <6 months ago
- •Portal vein thrombosis without signs of cavernous transformation or recanalization
- •Severe alcoholic hepatitis (Glasgow Alcoholic Hepatitis Score > 11)
- •Hepatic encephalopathy grade III-IV
- •Current, planned or previous treatment with direct antiviral agents for hepatitis C virus (HCV) in the last six months Contraindications for human albumin infusion (pulmonary oedema, hypersensitivity etc.)
- •Evidence of current malignancy except for non-melanocytic skin cancer and hepatocellular carcinoma within Barcelona Clinic Liver Cancer (BCLC)-0 or BCLC-A
- •Presence or history of severe extra-hepatic diseases (e.g.,chronic renal failure requiring hemodialysis, severe heart disease (NYHA > II); severe chronic pulmonary disease (GOLD Score ≥ C), severe neurological and psychiatric disorders, pulmonary arterial hypertension)
- •HIV positive or other condition associated with and/or requiring immunosuppression
- •Previous liver or other transplantation
- •Pregnancy
- •Breastfeeding
- •Patients who decline to participate, patients who cannot provide prior written informed consent due to other causes than hepatic encephalopathy or patients with hepatic encephalopathy who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker or sufficient ability to provide delayed informed consent
- •Physician's denial (investigator considers that the patient will not adhere to the study protocol scheduled, e.g. in case of heavy drinking)
- •Participation in another study within 3 months prior to screening
研究组 & 干预措施
High expected effect: Human Albumin 20% + Standard Medical Treatment
Participants stratified to a high expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions.
干预措施: Human albumin (Drug)
High expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment
Participants stratified to a high expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions.
干预措施: sodium chloride (Drug)
Low expected effect: Human Albumin 20% + Standard Medical Treatment
Participants stratified to a low expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions.
干预措施: Human albumin (Drug)
Low expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment
Participants stratified to a low expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions.
干预措施: sodium chloride (Drug)
结局指标
主要结局
Cumulative number of liver-related clinical outcomes
时间窗: 6 months
Cumulative number of liver-related clinical outcomes (variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury and overt hepatic encephalopathy) and TIPS (insertion or revision) with death and liver transplantation as counting and censoring events
次要结局
- The number of episodes of acute-on-chronic liver failures(6 months)
- Time to first hospital admission (in days)(180 days)
- Number of intensive care unit admissions(180 days)
- Number of large volume paracentesis(6 months)
- Health economic evaluation(6 months)
- Number of treatment-related adverse events(6 months)
- Time-to-first liver-related clinical outcome(6 months)
- Signatures associated with a poor prognosis as defined by the Microb-Predict biomarker(6 months)
- Incidence of variceal bleeding(6 months)
- 6-months survival(6 months)
- Number of organ failures(6 months)
- Change in CLDQ(6 months)
- Change in EQ-5D-5L(6 months)
- Number of hospital admissions(180 days)
- Analysis of the cost/effectiveness ratio(6 months)
- Incidence of hepatorenal syndrome acute kidney injury(6 months)
- Incidence of overt hepatic encephalopathy(6 months)
- Changes in serum albumin levels(6 months)
- Number of treatment-related serious adverse events(6 months)
- Incidence of refractory ascites(6 months)
- Incidence of spontaneous bacterial peritonitis(6 months)
- Incidence of acute kidney injury >= 1B(6 months)
- Incidence of infection requiring hospitalization(6 months)
- Incidence of liver transplantation(6 months)
- Change in SF-36(6 months)
- Days spent on hospitalization (in days)(180 days)
- Length of intensive care unit admissions (in days)(180 days)
- Incidence of TIPS insertion or revision(6 months)
研究者
Aleksander Krag
Professor
Odense University Hospital