Patients with advanced liver disease often has low serum albumin level. The Infusion of
human albumin is a standard of care after removal of ascitic fluid in patients with
cirrhosis with refractory ascites. The objective of the study is to prove that regular
infusion of albumin prevents formation of fluid in abdomen (ascites) or pleural fluid
(Hydrothorax) and thus reduces the requirement of paracentesis or thoracentesis, and
prevent complications.
The Primary endpoints are: (1) Number of paracentesis/thoracentesis needed and volume of
fluid removed per month and if there is any reduction in frequency or volume after
high-dose albumin administration; (2) Twelve-month mortality or transplant. Secondary
endpoints are: (1) Improvement of MELD score; (2) Cumulative diuretic dosage; (3)
Development of hyponatremia or hyperkalemia as potential diuretic-induced side-effects;
(4) Incidence of cirrhosis related complications (spontaneous bacterial peritonitis,
other bacterial infections, renal impairment, hepatorenal syndrome, hepatic
encephalopathy and gastrointestinal bleeding related to portal hypertension); (5) Quality
of life; (6) Number and duration of hospital admissions; and (7) Treatment
cost-effectiveness.
The research design is a prospective, parallel, randomized, open label clinical trial.
The target trial population comprises of patients with advanced cirrhosis. Eligible
patients will be randomized into either one of two categories: 1) the control group will
receive the standard of care (SOC) including moderate sodium restriction and maximal
daily tolerated doses of diuretics, and 2) the Intervention group will receive
intravenous human albumin at a dose (1g/kg, with minimum dose of 50g and maximum dose of
100g) weekly plus SOC.
In both groups, when large-volume paracentesis is needed, the patient will receive human
albumin in the dose of 6-8 g/L of ascites removed as SOC.
Inclusion Criteria:
Age > 18 years.
patients diagnosed with liver cirrhosis. Refractory ascites which is defined as
ascites failing to resolve after maximum tolerable dose of diuretics, and usually
require frequent paracentesis.
Exclusion Criteria:
Patients < 18y and patients with no history of liver cirrhosis
patients with refractory ascites but have trans-jagular intrahepatic portosystemic
shunts (TIPS) with previous 3 months
Patients with ascites due to other causes, including cardiac, malignant Procedure
Eligible patients will be identified by the PI and the research team. Participants
will be approached to participate in the study. The research coordinator will fully
explain the study procedures, and if the patient is willing to participate, he or
she will sign the informed consent. After signing the informed consent, eligible
patients will be randomly assigned into two groups: 1) the control arm will receive
the standard of care (SOC), including moderate sodium restriction, maximal daily
tolerated doses of diuretics, and post-paracentesis albumin, and 2) the intervention
group will receive intravenous human albumin at a dose of (1g/kg), with a minimum
dose of 50g and a maximum dose of 100g, plus SOC. patients will be randomly assigned
(1:1) to either of these two groups.
In both groups, when large-volume paracentesis is needed, the participant will receive
human albumin in the dose of 6-8 g/L of ascites removed.
No concomitant medications are withheld during the study. After enrollment, participants
will be assessed by a physician monthly for up to one year or study interruption or liver
transplant or death. In both groups with refractory ascites, most of the patient require
weekly or biweekly monitoring and paracentesis. The investigators plan to approach the
patients during these visits to get the consent and administer the extra albumin dose.
In each visit, ascites severity will be evaluated with hemodynamic status, weight, new
symptoms, and diuretic dose. Each visit may last 15 minutes or more.
Patients who consent to the study will complete a self-administered questionnaire to
assess health-related quality of life (using CLDQ, CLDQ-HCV and CLDQ- NASH
Questionnaires). Each patient response will be coded to ensure privacy, and the coded
data will be entered into a collection sheet with no protected health information (PHI)
gathered during the survey. The investigators will give the questionnaire: at the time of
enrollment and at the 6 and 12 month time points