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

Phase 2

Withdrawn

• Conditions: Liver Failure; Cirrhosis
• Interventions: Drug: Human derived Transfer factor; Drug: Aqua pro injectione 4ml ampules for subcutaneous injection

• Registration Number: NCT02837939
• Lead Sponsor: Martin Janičko

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-07-13
• Study First Submitted QC: 2016-07-15
• Study First Posted: 2016-07-20
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-15
• Last Update Posted: 2023-11-18
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Human derived Transfer factor	Drug: Human derived Transfer factor applied by subcutaneous injection in specified time points.
Control	Aqua pro injectione 4ml ampules for subcutaneous injection	Aqua pro injectione 4 mL ampules for subcutaneous administration in the same time points as in the active arm

Primary Outcome Measures

Name	Time	Method
Composite endpoint that includes the incidence specified infections:	Two years	1. Spontaneous bacterial peritonitis; 2. Urinary tract infections: 3. Pneumonia; 4. Skin and soft tissue infections; 5. Spontaneous bacteremia; 6. Endocarditis; 7. Tuberculosis; 8. Infectious colitis

Secondary Outcome Measures

Name	Time	Method
The usage of antibiotics required for treatment of a diagnosed infection	Two years
Length of hospital stay	Two years	The length of hospital stay after the admission with diagnosed infection or contraction of infection during hospital stay
The incidence of adverse effects	2 years

Trial Locations

Locations (1)

F.D.Roosevelt Teaching Hospital with policlinic Banska Bystrica; 🇸🇰 Banska Bystrica, Slovakia