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

Effects of Maintaining Steady Albumin Levels by Targeted Albumin Therapy (TAT 4) on Survival and Liver Related Complications in Cirrhosis With Ascites and Low Serum Albumin Level- a Randomized Controlled Trial

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.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Other: placebo; Drug: ALB Protein, Human

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 Type: Interventional
• Enrollment (Anticipated): 304
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Shasthry SM, MD; Phone Number: 01146300000; Email: shasthry@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Recruiting
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Shasthry SM, MD; Phone Number: 01146300000; Email: shasthry@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: placebo; placebo
Experimental: Albumin; 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	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplant/Transintrahepatic Portosystemic Shunt (TIPS) free survival in both groups	1 year survival	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Anticipated): September 10, 2019
• Primary Completion (Anticipated): August 8, 2020
• Study Completion (Anticipated): August 8, 2021

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites
• Other Study ID Numbers: ILBS-TAT4-01

Drug and device information, study documents

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