Effects of Maintaining Steady Albumin Levels (TAT 4) on Survival and Liver Related Complications in Cirrhosis With Ascites

Not Applicable

• Conditions: Liver Cirrhosis
• Interventions: Other: placebo; Drug: ALB Protein, Human

• Registration Number: NCT04058613
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

Investigators intend to assess the utility of regular albumin infusions to maintain a targeted serum albumin level of 4.0 g/dl in newly detected cirrhotic patients with low albumin levels (\<2.8g/dl) with ascites.

Detailed Description

Cirrhosis is characterized by progressive deterioration in liver functions. Liver's synthetic functions are inferred by serum albumin and INR estimation. Lower albumin level is a marker of severe liver disease and probability of worsening ascites, hepatorenal syndrome with increased risk for infections. Of the three recent RCTs on utility of long-term administration of albumin, two showed improvement in survival. The studies had included different patient populations (diuretic refractory ascites, high dose diuretics and patients on liver transplant waiting list) with different albumin infusion protocols and different end-points. These studies were done in advanced cases of cirrhosis. There is limited data on the utility of regular albumin infusions in early hepatic decompensation (albumin levels-\<2.8g/dl with ascites) and the effect of maintaining a targeted albumin level on survival or liver related side effects. Investigators are trying to address this issue by starting regular albumin infusions at an earlier stage of liver decompensation.

Study Timeline

• Study First Submitted: 2019-08-13
• Study First Submitted QC: 2019-08-14
• Study First Posted: 2019-08-15
• Status Verified: 2019-09
• Study Start: 2019-09-10
• Last Update Submitted: 2019-09-11
• Last Update Posted: 2019-09-12
• Primary Completion: 2020-08-08
• Study Completion: 2021-08-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 304

Inclusion Criteria

• Newly detected cirrhotic patients aged more than 18 years
• Cirrhosis defined by standard clinical, analytical and/or histological criteria
• Serum albumin level < 2.8g/dl with or without ascites
• Who would agree to give written informed consent

Exclusion Criteria

• Uncontrolled HTN (sys>150/ dis >90 mmHg) or h/o any drug therapy for HTN
• Prior h/o Transjugular Intrahepatic Portosystemic Shunt (TIPS)
• Hepatocellular Carcinoma
• Active alcohol abuse within 3 months
• Patients presenting as Acute on Chronic Liver Failure
• Extrahepatic organ failure
• Known case of chronic heart failure or respiratory failure
• Diagnosed Chronic Kidney Disease
• Patients with hydrothorax
• Prior liver transplant recipient
• Human Immunodeficiency Virus infection
• Use of albumin infusion in the last one month
• CTP>12, MELD>28
• Total Bilirubin >3 g/dl
• Overt Hepatic Encephalopathy at Presentation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo
Albumin	ALB Protein, Human	Albumin infusions will be given at a dose of 40 g twice weekly till a steady albumin level of 4.0g/dl is reached followed by 100ml of 20% albumin at least once in two weeks to maintain a steady albumin level of 4.0g/dl along with the standard medical therapy

Primary Outcome Measures

Name	Time	Method
Transplant/Transintrahepatic Portosystemic Shunt (TIPS) free survival in both groups	12 months	1 year survival

Secondary Outcome Measures

Name	Time	Method
Hepatic encephalopathy grade 3 or 4 in both groups	12 months	HE as per West Haven criteria
Number of new cases with gastrointestinal bleeding in both groups	12 months	gastrointestinal bleeding as confirmed by endoscopic/clinical evidence of variceal bleed.
Number of hospitalizations per subject in both groups	12 months	Need for any cause hospitalization
Spontaneous bacterial peritonitis [SBP] in both groups	12 months	Spontaneous bacterial peritonitis is defined as ascitic fluid absolute neutrophil count \> 250/ mL with or without culture positivity
Renal impairment in both groups	12 months	serum creatinine concentration \>1•5 mg/dL
Hepatorenal Syndrome in both groups	12 months	Hepatorenal Syndrome type 1 is defined as new onset increase in serum creatinine level by 0.3 mg/dL or 50% increase from baseline
Requirement of diuretics in both groups	12 months	Frusemide or Aldactone for management of ascites
New onset breathlessness/ Hypertension within 24 hours of albumin infusion in both groups	within 24 hours	Development of cardiac overload
New onset refractory ascites in both the groups	12 months	refractory ascites is defined as non response to maximum tolerated dose of diuretics
Requirement of paracentesis in both groups	12 months	Ascitic tapping for relieve of pressure symptoms or diagnosis of SBP
Quality of life by Ascite-Q questionnaire in both groups	12 months	semiquantitative questionnaire to be answered by the participants

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences; 🇮🇳 New Delhi, Delhi, India