AGRA Before and After Liver Transplantation

ID: NCT03446521
Status: Not yet recruiting
Phase: N/A
Start Date: April 01, 2018
First Submitted: February 19, 2018
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: Medical University of Graz
Location: N/A
Conditions: Liver Cirrhosis
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Study Description

Brief Summary

The immune system is impaired in liver cirrhotic patients, which is associated with a high risk for bacterial infections and worse outcome. A novel biomarker, acellular growth retardation ability (AGRA), can predict the development of severe infections in patients with liver cirrhosis and therefore identify patients at risk. It is still unclear, how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections. Therefore, AGRA will be measured before and after liver transplantation and predictive merit of AGRA for post-transplant infections will be tested.

Detailed Description

Cirrhosis-associated immune dysfunction syndrome (CAIDS) is a well-recognized phenomenon. It affects all immune cells as well as the humoral immune system. Because of this deficiency patients with liver cirrhosis often suffer from severe infections that can be complicated by sepsis, acute renal or liver failure, and lead to prolonged hospitalization and ultimately to the death of the patient. The humoral immune system is a first-line defence mechanism and consists of cell-free molecules that are partly produced by the liver and target pathogens through opsonisation, growth inhibition and lysis. A cirrhotic liver cannot reach its full protein expression capacity and consequently, quantitative and qualitative changes of complement factors and immunoglobulins have been observed in liver disease patients before.

Liver transplantation remains the only curative option to treat liver cirrhosis and its extrahepatic manifestations; however due to limited organ supply this option is not applicable in all cases. Therefore, liver cirrhosis and its complications (eg. infections) need to be managed by health care professionals, who often lack appropriate tools for risk assessment. To meet this clinical need, a novel biomarker was recently established (Acellular Growth Retardation Ability, short AGRA) that uses the state of the humoral immune system to predict the future occurrence of severe infection in liver disease patients. However, it is still unclear how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections.

Therefore, patients scheduled for liver transplantation will be included in the trial. AGRA measurements before and after the transplant (1, 7, 90 days after the end of antibiotic treatment) will be performed. Additionally outcome data regarding severe infections are collected for one year before and after transplantation. The respective organ donors are included as a control group.
Condition or disease Intervention/treatment Phase

Liver Cirrhosis

N/A

Tracking Information

First Submitted DateFebruary 19, 2018
Last Update Posted DateFebruary 23, 2018
Anticipated Start DateApril 01, 2018
Anticipated Completion DateApril 01, 2020
Anticipated Primary Completion DateApril 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change of Acellular growth retardation ability (AGRA) [Time Frame: change from transplantation to 90 days after the end of prophylactic antibiotic treatment after the transplantation]

    Functional biomarker for the state of the humoral immune system

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Infections [Time Frame: 1 year after transplantation]

    Occurrence of severe infections

  • Infections [Time Frame: 1 year before transplantation]

    Occurrence of severe infections

  • Complications [Time Frame: during hospital stay]

    Occurrence of transplantation-related complications

  • C reactive protein [Time Frame: change from transplantation to 90 days after the end of prophylactic antibiotic treatment after the transplantation]

    routine biomarker for infections

  • Liver function [Time Frame: before transplantation]

    State of the donated liver, including results of a possible liver biopsy prior to transplantation

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleAGRA Before and After Liver Transplantation
Official TitleHumoral Immune Status in Patients With Liver Cirrhosis Before and After Liver Transplantation
Brief Summary

The immune system is impaired in liver cirrhotic patients, which is associated with a high risk for bacterial infections and worse outcome. A novel biomarker, acellular growth retardation ability (AGRA), can predict the development of severe infections in patients with liver cirrhosis and therefore identify patients at risk. It is still unclear, how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections. Therefore, AGRA will be measured before and after liver transplantation and predictive merit of AGRA for post-transplant infections will be tested.

Detailed Description

Cirrhosis-associated immune dysfunction syndrome (CAIDS) is a well-recognized phenomenon. It affects all immune cells as well as the humoral immune system. Because of this deficiency patients with liver cirrhosis often suffer from severe infections that can be complicated by sepsis, acute renal or liver failure, and lead to prolonged hospitalization and ultimately to the death of the patient. The humoral immune system is a first-line defence mechanism and consists of cell-free molecules that are partly produced by the liver and target pathogens through opsonisation, growth inhibition and lysis. A cirrhotic liver cannot reach its full protein expression capacity and consequently, quantitative and qualitative changes of complement factors and immunoglobulins have been observed in liver disease patients before.

Liver transplantation remains the only curative option to treat liver cirrhosis and its extrahepatic manifestations; however due to limited organ supply this option is not applicable in all cases. Therefore, liver cirrhosis and its complications (eg. infections) need to be managed by health care professionals, who often lack appropriate tools for risk assessment. To meet this clinical need, a novel biomarker was recently established (Acellular Growth Retardation Ability, short AGRA) that uses the state of the humoral immune system to predict the future occurrence of severe infection in liver disease patients. However, it is still unclear how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections.

Therefore, patients scheduled for liver transplantation will be included in the trial. AGRA measurements before and after the transplant (1, 7, 90 days after the end of antibiotic treatment) will be performed. Additionally outcome data regarding severe infections are collected for one year before and after transplantation. The respective organ donors are included as a control group.

Study TypeObservational
Study PhaseN/A
Estimated Enrollment
108
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Liver Cirrhosis
Target Follow-Up Duration N/A
Biospecimen:
Retention: Samples Without DNA
Description: Serum
Sampling MethodNon-Probability Sample
Study PopulationPatients listed for liver transplantation at the University Hospital in Graz, Austria for any reason will be included in the study. The respective donors will serve as a control cohort.
Intervention
Not Available
Study Groups/Cohorts
Test group
Patients undergoing liver transplantation, no intervention (study-specific) is planed

Control Group
Respective organ donors of the included liver recipients, no intervention (study-specific) is planed

Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment108
Completion DateApril 01, 2020
Eligibility Criteria: Inclusion Criteria:
- Patients between 18-80 years
- Listed for liver transplantation (for recipients)
- Liver recipient is included in the study (for donors)
- Informed consent

Exclusion Criteria:
- Antibiotic therapy with substances active against E. coli at the scheduled blood sampling
GenderAll
Age18 Years to 80 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Not Available

Administrative Information

NCT Number:NCT03446521
Other Study ID Numbers
AGRA-TX
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Medical University of Graz
Collaborators
Not Available
Investigators
Not Available