Early Postoperative CRRT After Liver Transplantation in ACLF Patients With Overt HE

Study Overview
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Brief Summary
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Pretransplant hepatoencephalopathy (HE) markedly impacts recipient outcomes after liver transplantation. Intraoperative CRRT showed benefits but feasibility was much concerned. This study aims to observe the effect on consciousness recovery when initiating CRRT early in the post-transplant period in recipients with ACLF and overt HE.

Detailed Description
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Hepatoencephalopathy (HE) is a common severe decompensation in end stage liver diseases and resulted to the need of liver transplantation (LT). Pretransplant HE markedly impacts recipient outcomes after liver transplantation. HE in acute on chronic liver failure (ACLF) is categorized to type C HE. Hyperammonemia and systemic inflammation have been reported to contribute its development. Continuous renal replacement therapy (CRRT) has been shown great benefits in ACLF patients with HE. Intraoperative CRRT in LT also showed benefits but feasibility was much concerned. Our preliminary retrospective data showed that early CRRT (eCRRT) after LT reduced consciousness recovery time, ventilation days and post-transplant infection rate. This open label, parallel randomized trial will observe the effect on consciousness recovery when initiating CRRT early (eCRRT) in the post-transplant period in recipients with ACLF and overt HE. The CRRT safety and ventilation days, infection, mortality and ICU stay will also be measured.

Official Title
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Early Postoperative Continuous Renal Replacement Therapy After Liver Transplantation in Acute-on-chronic Liver Failure Patients With Overt Hepatic Encephalopathy

Conditions
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Acute-On-Chronic Liver Failure, Hepatic Encephalopathy

Intervention / Treatment
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* Device: eCRRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver transplant recipients who meet all of the following criteria will be enrolled Pre transplant liver failure: Total bilirubin over 171μmol/L and prothrombin activity (PTA)<40%; Overt hepatic encephalopathy(HE): Grade II or higher HE according West Haven classification; HE associated with acute liver failure (Type A) or cirrhosis complicated with portal hypertension and/or portal systemic shunts (Type C) Exclusion Criteria: Patients with a previous history of kidney-related diseases and glomerular filtration rate <30 millilitre per minute; Patients with acute renal failure need CRRT before transplantation; Patients newly developed acute renal failure need CRRT at the time of randomization; Retransplantation or multiple-organs transplantation; Any ischemic or hemorrhagic stroke co-morbidity; Hemodynamic instability requiring fluid resuscitation or very high dose of vasopressors; Extremely moribund patients with an expected life expectancy of less than 24 hours.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: eCRRT group<br>Initiated CRRT within the first 24 post-transplant hours. | Device: eCRRT<br>* eCRRT was define as: Initiated within the first 24 post-transplant hours; High volume (35-50ml/kg) hemofiltration; Continuous at least 12 hours per day for 3 days; Standard treatment<br>|
| No Intervention: Control group<br>Standard treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consciousness recovery time | The period from post-transplant immediate to the time when the patient have the first spontaneous eye opening and proper motor response to commands. | From the immediate to 30 days after liver transplantation | 
| Adverse events | Any adverse event which probable related with CRRT | From the immediate to 7 days after liver transplantation (CRRT therapy period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive ventilation days | The time period when patients breath with ventilator through artificial airway | From the immediate to 30 days after liver transplantation | 
| ICU stay (days) | The time period from transplantation to first ICU discharge | up to one year | 
| Reintubation rate | Reintubation after the first extubation following liver transplantation | From the immediate to 30 days after liver transplantation | 
| 90 days mortality | All cause mortality | From the immediate to 90 days after liver transplantation | 
| Infection rate | Any diagnosed infection after transplantation in 30 days | From the immediate to 30 days after liver transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute-On-Chronic Liver Failure, Overt Hepatic Encephalopathy, Continuous Replacement Renal Therapy, Liver Transplantation