Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction

Study Overview
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Brief Summary
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This study is aimed to assess the efficacy of Human derived Transfer factor ( T-lymphocytes homogenate that contains small molecular weight (10 kDa) molecules: various IFNs, ILs, chemokines, endorfins, heat shock proteins) in decreasing rate and/or severity of infections in acute or chronic decompensations of liver cirrhosis and acute on chronic liver failure..

Detailed Description
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Most of mortality from advanced chronic liver disease (ACLD) is mediated by so- called specific complications of end-stage liver disease (ESLD); one of the most important is infection (25-30%). Infection is responsible for considerable proportion of ESLD-related mortality. Important in pathogenesis of infections in ESLD is CAIDS (cirrhosis - associated immune dysfunction syndrome), recently re-named to CAID (Cirrhosis-Associated Immune Deficit). TRANSFER FACTOR (TF) is supposed to act at several points in CAID - cascade. This gave rise to hypothesis, that TF could be of benefit in AD/ACLF. Characteristics of TF It has been shown that transmission fo T-Lymphocyte reactivity is transmissible not only by T-cells alone, but also by hommogenate of peripheral white blood cells. Later it became clear that for the transmission of cellular immunity is responsible dialysable fraction of T-lymphocytes homogenate (with small molecular weight of 10 kDa; consists of amino acids, small peptides, nucleotides etc). This homogenate was named Transfer - factor (TF). One dose of lyophilized drug contains: Leucocyti dialysatum 200 x 10 6 (contains various IFNs, ILs, chemokines, endorfins, heat shock protein etc) stimulates T H 1 response induces production of IL-1, IL-2 activates chemotaxis of immunocompetent cells increases fagocytic activity activates antigen-presentation by APCs The aim of this study is to assess the efficacy of transfer factor in decreasing rate and/or severity of infections in ACLF.

Official Title
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Prospective Randomized Single-blind Study on Transfer-factor in Acute Decompensation of Advanced Chronic Liver Disease and Acute-on-chronic Liver Failure.

Conditions
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Cirrhosis, Liver Failure

Intervention / Treatment
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* Drug: Human derived Transfer factor
* Drug: Aqua pro injectione 4ml ampules for subcutaneous injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: admission to hospital at participating liver units or ICUs or internal medicine wards with acute decompensation (AD) of advanced chronic liver disease or acute-on-chronic liver failure according to CLIF - C criteria ability to provide informed consent, Exclusion Criteria: disapproval lymphoproliferative disorders liver transplantation in the past pregnancy suspected. chronic infection in risk locations CNS peritoneum Known virus-related immune deficiency malignancy severe heart failure (NYHA >= III) severe lung disease (COPD, GOLD>3)

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Drug: Human derived Transfer factor applied by subcutaneous injection in specified time points. | Drug: Human derived Transfer factor<br>* One dose (the content of one amp.) of lyophilised drug contains: Leucocyte dialysatum 200 x 10 to the power of 6 (Lyophilized dialysate from 200 million leukocytes) pH = 7.8 to 9 after reconstitution (dissolving) of drug To be administered subcutaneously as follows: 12 doses TF in total: 3 x TF in first week: day 1,3,5 2 x TF in week 2: day 8 , 11 1 xTF in week 3 and 4 : day 15, 22 1 x TF once a month up to 6 month<br>* Other names: IMMODIN. Holder: IMUNA PHARM a.s. - GRIFOLS (SVK) Registration number: 59/0147/89-CS;|
| Placebo Comparator: Control<br>Aqua pro injectione 4 mL ampules for subcutaneous administration in the same time points as in the active arm | Drug: Aqua pro injectione 4ml ampules for subcutaneous injection<br>* 12 doses in total: 3 doses in first week: day 1,3,5 2 doses in week 2: day 8 , 11 1 dose in week 3 and 4 : day 15, 22 1 dose once a month up to 6 month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint that includes the incidence specified infections: | Spontaneous bacterial peritonitis Urinary tract infections: Pneumonia Skin and soft tissue infections Spontaneous bacteremia Endocarditis Tuberculosis Infectious colitis | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | The length of hospital stay after the admission with diagnosed infection or contraction of infection during hospital stay | Two years | 
| The usage of antibiotics required for treatment of a diagnosed infection |  | Two years | 
| The incidence of adverse effects |  | 2 years |