A Phase 2b Study to Evaluate Safety and Efficacy of LifeLiver (Bio Artificial Liver) in Acute or Acute-on-Chronic Liver Failure Patients Waiting Emergent Liver Transplantation
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Survival rate for 30 days
研究概览
简要总结
This is a prospective, comparative, open label, phase 2b study designed to investigate the safety and efficacy of LifeLiver (an Extracorporeal Bio Artificial Liver). The study will recruit approximately 40 acute or acute-on-chronic liver failure patients.
详细描述
Patient should have acute or acute-on-chronic liver failure and be registered in KONOS (Korean Network for Organ Sharing) system as a candidate of liver transplantation. Patients who meet the eligibility criteria will be assigned to control group or experimental group. Experimental group patients will receive LifeLiver treatment in addition to the best supportive care for the disease.
Primary Objective:
- To evaluate the efficacy of LifeLiver in terms of a comparison of 30 day-survival rate between control group and experimental group. (after patient's KONOS (Korean Network for Organ Sharing) registration date)
Secondary Objective:
- To compare a median value of 2 week-survival rate and duration of survival between both study groups
- Survival analysis respect to each group of patients divided according to the KONOS status
- To investigate safety and change of overall efficacy indicators in terms of Glasgow Coma Scale, West Heaven Criteria for hepatic encephalopathy, MELD (Model for End-stage Liver Disease) score, blood ammonia, inflammatory cytokine
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 60 years of age
- •Acute or acute-on-chronic liver failure patients who is waiting for liver transplantation (KONOS liver transplant emergency grade 2 or 3)
- •Hepatic encephalopathy grade II or above
- •The following laboratory values must be documented within the screening period:
- •INR (international normalized ratio) 2.0 or above
- •Serum ammonia 56 micromole/L or above
- •Total bilirubin 5mg/dL or above
- •Body weight 45kg or above
- •Patient who can not expect effective treatment or prolonged survival
- •Patient or patient's legal representative willing to provide informed consent and commit to study procedures
排除标准
- •Patient who has contraindication to plasmapheresis
- •Severe hypotension (systolic blood pressure 80mmHg or less)
- •Platelet < 15,000/mm3
- •Contraindications to liver transplantation (sepsis, severe heart disease, uncontrollable hemorrhage, irreversible brain damage)
- •Cerebral hemorrhage
- •Positive HIV infection
- •Serious or life-threatening hemorrhage just before initiation of the study
- •Patients with high gastrointestinal bleeding tendency (a history or suspicion of gastrointestinal bleeding within last 3 months)
- •Hepatocellular carcinoma patient with 7 (or more) tumors or a 6cm (or larger) diameter single tumor
- •Pregnant or lactating women
- •Antibiotics (beta-lactam family) hypersensitive and streptomycin, amphotericin B sensitive patients
- •Patients with inappropriate condition to participate the study under investigator's judgement
结局指标
主要结局
Survival rate for 30 days
时间窗: up to 30 days
To compare survival rate of LifeLiver treatment with best supportive care
Occurrence of clinical safety laboratory adverse events (AEs)
时间窗: up to approximately 12 months
To compare occurrence of clinical safety laboratory adverse events between Experimental group and Control group assessed according to NCI-CTCAE v5.0
Incidence of transition of PERV (Porcine Endogenous Retrovirus) (for experimental group only)
时间窗: up to approximately 12 months
Number of reported PERV transition defined as viral detection in subject's blood by PCR (Polymerase Chain Reaction) test.
次要结局
- Comparison of subject's neurological status - hepatic encephalopathy grade(up to approximately 12 hours after completion of LifeLiver treatment)
- Comparison of subject's neurological status - Glasgow Coma Scale(up to approximately 12 hours after completion of LifeLiver treatment)
- Survival rate for 14 days(up to 14 days)
- Median value of duration of survival(up to approximately 12 months)
- Kaplan-Meier estimate of subjects with MELD (Modell for End-stage Liver Disease) score >37(up to 30 days)
- Kaplan-Meier estimate of subjects with 31≤ MELD score ≤37(up to 30 days)
- Comparison of MELD score(up to approximately 12hours after completion of LifeLiver treatment)
- Comparison of subject's value of inflammatory cytokines(up to approximately 12 hours after completion of LifeLiver treatment)
- Comparison of subject's value of blood ammonia(up to approximately 12 hours after completion of LifeLiver treatment)