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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04058613
• Other study ID #: ILBS-TAT4-01
• Status: Recruiting
• Phase: N/A
• Start date: September 10, 2019
• Est. completion date: August 8, 2021

Study information

• Verified date: September 2019
• Source: Institute of Liver and Biliary Sciences, India
• Contact: Dr Shasthry SM, MD
• Phone: 01146300000
• Email: shasthry[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 304
• Est. completion date: August 8, 2021
• Est. primary completion date: August 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly detected cirrhotic patients aged more than 18 years

• Cirrhosis de?ned 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

Related Conditions & MeSH terms

• Ascites
• Fibrosis
• Liver Cirrhosis

Intervention

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

Other:
• placebo
placebo

Locations

Country	Name	City	State
India	Institute of Liver & Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplant/Transintrahepatic Portosystemic Shunt (TIPS) free survival in both groups	1 year survival	12 months
Secondary	New onset refractory ascites in both the groups	refractory ascites is defined as non response to maximum tolerated dose of diuretics	12 months
Secondary	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
Secondary	Renal impairment in both groups	serum creatinine concentration >1•5 mg/dL	12 months
Secondary	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
Secondary	Hepatic encephalopathy grade 3 or 4 in both groups	HE as per West Haven criteria	12 months
Secondary	Number of new cases with gastrointestinal bleeding in both groups	gastrointestinal bleeding as confirmed by endoscopic/clinical evidence of variceal bleed.	12 months
Secondary	Requirement of paracentesis in both groups	Ascitic tapping for relieve of pressure symptoms or diagnosis of SBP	12 months
Secondary	Requirement of diuretics in both groups	Frusemide or Aldactone for management of ascites	12 months
Secondary	Number of hospitalizations per subject in both groups	Need for any cause hospitalization	12 months
Secondary	New onset breathlessness/ Hypertension within 24 hours of albumin infusion in both groups	Development of cardiac overload	within 24 hours
Secondary	Quality of life by Ascite-Q questionnaire in both groups	semiquantitative questionnaire to be answered by the participants	12 months