Clinical trial NCT03882346: Study to Evaluate Safety and Efficacy of LifeLiver in Acute or Acute-on-Chronic Liver Failure Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Liver Failure
Acute-On-Chronic Liver Failure
Keywords: Acute Liver Failure
Acute-On-Chronic Liver Failure
Artificial Liver
Liver Transplantation
Lead sponsor: HLB Cell Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-03-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel, open label study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1. 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:

1. To compare a median value of 2 week-survival rate and duration of survival between both study groups
2. Survival analysis respect to each group of patients divided according to the KONOS status
3. 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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Survival rate for 30 days
timeFrame: up to 30 days
measure: Occurrence of clinical safety laboratory adverse events (AEs)
timeFrame: up to approximately 12 months
measure: Incidence of transition of PERV (Porcine Endogenous Retrovirus) (for experimental group only)
timeFrame: up to approximately 12 months
Secondary outcomes:
measure: Survival rate for 14 days
timeFrame: up to 14 days
measure: Median value of duration of survival
timeFrame: up to approximately 12 months
measure: Kaplan-Meier estimate of subjects with MELD (Modell for End-stage Liver Disease) score >37
timeFrame: up to 30 days
measure: Kaplan-Meier estimate of subjects with 31≤ MELD score ≤37
timeFrame: up to 30 days
measure: Comparison of MELD score
timeFrame: up to approximately 12hours after completion of LifeLiver treatment
measure: Comparison of subject's neurological status - hepatic encephalopathy grade
timeFrame: up to approximately 12 hours after completion of LifeLiver treatment
measure: Comparison of subject's neurological status - Glasgow Coma Scale
timeFrame: up to approximately 12 hours after completion of LifeLiver treatment
measure: Comparison of subject's value of blood ammonia
timeFrame: up to approximately 12 hours after completion of LifeLiver treatment
measure: Comparison of subject's value of inflammatory cytokines
timeFrame: up to approximately 12 hours after completion of LifeLiver treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Dong Hyun Sinn, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: