Albumin Infusion in Inpatients With Decompensated Cirrhosis

Effect of Albumin Infusion in Patients With Decompensated Cirrhosis Hospitalized for Treatment of Complications of Liver Disease

Albumin infusion in patients with hospitalized decompensated, even in short-term period use, could improve survival through the reduction of systemic inflammation, which is the main driver of acute-on-chronic liver failure in cirrhosis. The effects could be highly associated with the albumin dosage. A comprehensive evaluation of the inflammation response by robust measurement is needed to prove insights into the therapeutic implications of albumin infusion.

The purpose of this study is to compare the effects of different amount of human albumin infusion per week in patients with hospitalized decompensated cirrhosis on 28-day transplant-free survival and to further compare the alleviation of inflammation, reduction of incidence of nosocomial infection, spontaneous bacterial peritonitis (SBP), acute kidney injury (AKI), acute-on-chronic liver failure (ACLF), and 90-day transplant-free survival. This will be a multicenter, national, retrospective study. There will be no randomization in this retrospective study. All patients who meet the inclusion criteria and not the exclusion criteria will be enrolled. All identified patients who meet criteria will be given an ID number comprised of a site number and patient number.

Study Overview

• Status: Not yet recruiting
• Conditions: Decompensated Cirrhosis; Acute-On-Chronic Liver Failure
• Intervention / Treatment: Drug: Albumin infusion

Detailed Description

Patients with decompensated cirrhosis frequently develop various complications, be it related to salt and water retention, renal dysfunction, hepatic encephalopathy, portal hypertensive bleeds, or various infections. These lead to frequent hospital admissions, impaired quality of life, and increased morbidities and mortality.

Although recent investigations have helped to elucidate the pathogenetic mechanisms that lead to the development of these complications, exactly how much each of these pathogenetic mechanisms contributes to the development of these complications is not clear. Among them, hypoalbuminemia has long been considered a cardinal feature of decompensated cirrhosis.

Human albumin is the main modulator of fluid distribution among the body compartments and also exerts many other biological properties unrelated to its oncotic power including antioxidation, immune modulation and anti-inflammatory effect, and endothelial stabilization as well as vascular integrity. Albumin infusion has been recommended by international guidelines after large-volume paracentesis in patients with ascites, or in spontaneous bacterial peritonitis to prevent and treat the hepatorenal syndrome. Long-term prophylactic administration of albumin to outpatients with prior history of ascites is also effective in preventing further complications and improving survival. A subsequent study suggests an anti-inflammatory effect of albumin in patients with cirrhosis; this finding suggests that infusions of albumin might increase survival by limiting systemic inflammation.

These promising data suggested a disease-modifying agent role of albumin in patients with decompensated cirrhosis. The investigators, therefore, hypothesized that albumin infusion in patients with hospitalized decompensated, even in short-term period use, could also improve survival through the reduction of systemic inflammation, which is the main driver of acute-on-chronic liver failure in cirrhosis. The effects could be highly associated with the albumin dosage. A comprehensive evaluation of the inflammation response by robust measurement is needed to prove insights into the therapeutic implications of albumin infusion.

To test these hypotheses, the investigators planned to perform retrospective analysis in two established cohorts of hospitalized decompensated cirrhosis: 1) the "RJH" cohort of decompensated cirrhosis in Ruijin Hospital enrolled between 2016 and 2018; 2) an established cohort of inpatients with cirrhosis enrolled from 23 centers in China between 2018 and 2019 (the "SONIC" study).

• Study Type: Observational
• Enrollment (Anticipated): 564

Contacts and Locations

• Study Contact: Name: Qing Xie, M.D. Ph.D.; Phone Number: 86-13651804273; Email: xieqingrjh@163.com
• Study Contact Backup: Name: Zhujun Cao, M.D. Ph.D.; Phone Number: 15216652990; Email: estherlucifer@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Target population is hospitalized patients with decompensated cirrhosis. For the purpose of this study, two established prospect cohorts will be used retrospectively including the "RJH" cohort and the "SONIC" cohort. All patients in the abovementioned cohorts had at least one of the following events for inclusion: overt ascites, active gastrointestinal bleeding, hepatic encephalopathy, bacterial/fungal infection, or jaundice.

Description

Inclusion Criteria:

Patients with decompensated cirrhosis nonelective admitted for overt ascites, active gastrointestinal bleeding, hepatic encephalopathy, bacterial/fungal infection, or jaundice, etc.

Exclusion Criteria:

1. Age below 16 or over 80 years
2. Lactation/ Pregnancy women
3. HIV infection
4. Admitted for scheduled procedures (e.g., band ligation, splenectomy, transjugular intrahepatic portosystemic shunting, liver biopsy) or reexamination or multidisciplinary consultation)
5. Hepatocellular carcinoma (HCC) outside Milan criteria or other disseminated malignancies
6. Previous liver transplantation
7. With previously known severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease; severe chronic pulmonary disease, psychiatric disorders)
8. Taking immunosuppressive or anticoagulation drugs for the treatment of extra-hepatic disease.
9. Patient' s refusal to participation
10. Failure to provide prior informed consent or with documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High-dose group; Total Intravenous albumin infusion >1.5g/kg per week while hospitalization	Drug: Albumin infusion; Albumin infusion was administrated according to the standard clinical practice
Medium-dose group; Total Intravenous albumin infusion 1.0 to 1.5g/kg per week while hospitalization	Drug: Albumin infusion; Albumin infusion was administrated according to the standard clinical practice
Low-dose group; Total Intravenous albumin infusion <1.0g/kg per week while hospitalization	Drug: Albumin infusion; Albumin infusion was administrated according to the standard clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplant-free survival at day 28 since enrollment	Transplant-free survival at day 28 since enrollment	From enrollment (Day 1) to Day-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of inflammatory markers from baseline	Changes of the level of each measured inflammatory marker (IL6, IL-8, TNF-a, etc.) at Day 7 and Day 14 as compared to the baseline level.	From baseline (sample collection date) to Day 7 and Day 14, respectively
Cumulative incidence of nosocomial infection by day 28	Cumulative incidence of nosocomial infection by day 28	From enrollment (Day 1) to Day-28
Cumulative incidence of SBP by day 28	Cumulative incidence of SBP by day 28	From enrollment (Day 1) to Day-28
Cumulative incidence of AKI by day 28	Cumulative incidence of AKI by day 28	From enrollment (Day 1) to Day-28
Cumulative incidence of ACLF by day 28	Cumulative incidence of ACLF by day 28	From enrollment (Day 1) to Day-28
Transplant-free survival at day 90 since enrollment	Transplant-free survival at day 90 since enrollment	From enrollment (Day 1) to Day-90

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2023
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: January 8, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Prognosis; Systemic inflammation; Albumin; decompensated cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Pathologic Processes; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Fibrosis; Liver Failure; Acute-On-Chronic Liver Failure; Liver Cirrhosis
• Other Study ID Numbers: RJH-Albumin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No