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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute-On-Chronic Liver Failure; Hepatic Encephalopathy
• Intervention / Treatment: Device: eCRRT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huimin Yi, doctor; Phone Number: 18922102510; Email: ylhmin@hotmail.com
• Study Contact Backup: Name: Haijin Lv, doctor; Phone Number: 18922103230; Email: haijinlv@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Liver transplant recipients who meet all of the following criteria will be enrolled

1. Pre transplant liver failure: Total bilirubin over 171μmol/L and prothrombin activity (PTA)<40%;
2. Overt hepatic encephalopathy(HE): Grade II or higher HE according West Haven classification;
3. HE associated with acute liver failure (Type A) or cirrhosis complicated with portal hypertension and/or portal systemic shunts (Type C)

Exclusion Criteria:

1. Patients with a previous history of kidney-related diseases and glomerular filtration rate <30 millilitre per minute;
2. Patients with acute renal failure need CRRT before transplantation;
3. Patients newly developed acute renal failure need CRRT at the time of randomization;
4. Retransplantation or multiple-organs transplantation;
5. Any ischemic or hemorrhagic stroke co-morbidity;
6. Hemodynamic instability requiring fluid resuscitation or very high dose of vasopressors;
7. Extremely moribund patients with an expected life expectancy of less than 24 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: eCRRT group; Initiated CRRT within the first 24 post-transplant hours.	Device: eCRRT; 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
NO_INTERVENTION: Control group; Standard treatment.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Huimin Yi, MD, The 3rd affiliated hospital of Sun Yat-sen University

Publications and helpful links

General Publications

• Yi H, Lv H, An Y, Yi X, Wei X, Chen G (2015) Early Continuous Blood Purification(CBP) Deceased the Incidence of Pulmonary Infection after Liver Transplantation in Severe End-Stage-Liver-Disease Recipients With Hepatic Encephalopathy. Transplantation 99:201-201

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2020
• Primary Completion (ANTICIPATED): May 31, 2022
• Study Completion (ANTICIPATED): August 31, 2022

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (ACTUAL): March 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Acute-On-Chronic Liver Failure; Liver Transplantation; Overt Hepatic Encephalopathy; Continuous Replacement Renal Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Liver Failure, Acute; Brain Diseases, Metabolic; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: LTeCRRT-P1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All the individual participant data (IPD) that underlie results in a publication will be shared with other researchers.
• IPD Sharing Time Frame: One year from the time of result publication
• IPD Sharing Access Criteria: Claim from Principle investigator by email. Need Curriculum Vitae.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No