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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: ALB Protein, Human
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albumin<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: placebo<br>* placebo<br>|

What is the study measuring?
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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 |