Clinical trial NCT05719051: Albumin Infusion in Inpatients With Decompensated Cirrhosis
Official title: Effect of Albumin Infusion in Patients With Decompensated Cirrhosis Hospitalized for Treatment of Complications of Liver Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Decompensated Cirrhosis
Acute-On-Chronic Liver Failure
Keywords: Albumin
decompensated cirrhosis
Systemic inflammation
Prognosis
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 564
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Transplant-free survival at day 28 since enrollment
timeFrame: From enrollment (Day 1) to Day-28
Secondary outcomes:
measure: Changes of inflammatory markers from baseline
timeFrame: From baseline (sample collection date) to Day 7 and Day 14, respectively
measure: Cumulative incidence of nosocomial infection by day 28
timeFrame: From enrollment (Day 1) to Day-28
measure: Cumulative incidence of SBP by day 28
timeFrame: From enrollment (Day 1) to Day-28
measure: Cumulative incidence of AKI by day 28
timeFrame: From enrollment (Day 1) to Day-28
measure: Cumulative incidence of ACLF by day 28
timeFrame: From enrollment (Day 1) to Day-28
measure: Transplant-free survival at day 90 since enrollment
timeFrame: From enrollment (Day 1) to Day-90
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: