Coagulation Parameters With Albumin in Decompensated Cirrhosis (CoPA-D).

Study Overview
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Brief Summary
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Albumin is commonly used plasma expander in patients of decompensated cirrhosis and has been found to have many beneficial effects, with few studies showing that maintenance of serum albumin levels above 3 g/dl has improved outcomes and mortality leading to widespread utilization in patients with cirrhosis of the liver. While 20% human albumin solution has been subject to in-depth analysis along several fronts, it's effects on coagulation parameters is unknown. With cirrhosis being a state of dysregulated clotting and bleeding, it is imperative to know the effects of such a widely used plasma expander on coagulation. The aim of this study is to evaluate the effects of albumin on coagulation parameters in patients of decompensated cirrhosis.

Detailed Description
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Aim and Objective: To study the effects of 20% human albumin infusions on coagulation parameters in patients with decompensated cirrhosis of the liver. Methodology: - Study population: All patients aged ≥ 18 years and ≤ 70 years admitted in Institute of Liver and Biliary Sciences, New Delhi with decompensated cirrhosis of any cause and S. Albumin ≤ 2.5 g/dl upon presentation and are giving written consent for participation in the study. Study design - Single center, Open label, Randomized controlled trial Study period - 1 year Monitoring and assessment - ABG prior to enrollment Investigations - tests performed on Day 0, 1, 3, 5 and 7 or till discharge (whichever is earlier) Routine: CBC, RFT, LFT, apTT, PT/INR, CXR Coagulation parameter: ROTEM (EXTEM, FIBTEM), Fibrinogen Inflammatory markers: ESR, CRP, IL-6, TNF-⍺ Endothelial dysfunction: vWF, ADAMTS-13 Cardiac function: NT-proBNP, PRA 2 D Echo,PFT with DLCO will be done at 0,1 and 7 days. Statistical Analysis: The data will be represented as mean±SD. The categorical data will be analysed using Chi-square test. The continuous data will be analysed by student T test, or Mann-Whitney test, whichever is applicable. Besides this, Cox regression will be applied to analyse the variables. For all tests, p≤ 0.05 will be considered statistically significant. Adverse effects Allergic reactions to albumin. Features of symptomatic volume overload. Stopping rule Day 7, or discharge (whichever is earlier) Allergic reaction to albumin Features of symptomatic volume overload Variceal bleeding Requirement of coagulation correct Expected outcome of the project: Derangement of ROTEM in the group of patients receiving human albumin solution

Official Title
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Coagulation Parameters With Albumin in Decompensated Cirrhosis (CoPA-D): An Open-label Randomized Control Trial

Conditions
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Decompensated Cirrhosis

Intervention / Treatment
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* Biological: Albumin
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years and ≤ 70 years Decompensated cirrhosis of any cause S. Albumin ≤ 2.5 g/dl upon presentation Written informed consent Exclusion Criteria: Patients of ACLF Patients admitted with proven indications for albumin (SBP, HRS, LVP) Advanced HCC Presence of hypotension PF ratios ≤ 300 mmHg on arterial blood gas IVC Collapsibility Index < 20% Albumin infusion within the past 3 weeks Post liver transplant patients AKI or CKD Known or suspected cardiac dysfunction Acute GI Bleed Severe Anemia Pregnant women PLHA Severe psychiatric disorders Lack of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albumin<br>20% human albumin solution infusion, to raise and maintain serum albumin levels above 3.0 g/dl. Human albumin solution will be given to those enrolled in the study having serum albumin levels ≤ 3 g/dl to maintain the serum albumin levels above 3 g/dl. | Biological: Albumin<br>* 20% human albumin solution infusion, to raise and maintain serum albumin levels above 3.0 g/dl. Human albumin solution will be given to those enrolled in the study having serum albumin levels ≤ 3 g/dl to maintain the serum albumin levels above 3 g/dl.<br>|
| Active Comparator: Standard of Care<br>Standard treatment that the patient would receive had they not been included in the trial. | Other: Standard of Care<br>* Standard treatment that the patient would receive had they not been included in the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clotting time in both groups. | coagulation parameters based on ROTEM | 1 week | 
| Change in clot formation time in both groups. | coagulation parameters based on ROTEM | 1 week | 
| Change in maximum clot formation in both groups. | coagulation parameters based on ROTEM | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in inflammatory parameters like ESR. |  | 7 days | 
| Changes in inflammatory parameters like CRP. |  | 7 days | 
| Changes in inflammatory parameters like IL-6 |  | 7 days | 
| Changes in inflammatory parameters like TNF-alpha. |  | 7 days | 
| Changes in endothelial dysfunction like VWF. |  | 7 days | 
| Changes in endothelial dysfunction like ADAMTS-13. |  | 7 days | 
| Effect on pulmonary function by Pulmonary function test with diffusing capacity of the lungs for carbon monoxide (DLCO). |  | 7 days | 
| Effect on renal function by s.creatinine. |  | 7 days | 
| Adverse effects of Human Albumin Solution |  | 7 days | 
| Change in the albuminome in both the groups | Albumin bound metabolites and lipids will be studied and the effect of albumin infusion on this albuminome. | 7 days | 
| Duration of hospital stay |  | 28 days | 
| Mortality at 28 days |  | 28 days |