Peri-operative rATG-perfusion of Solid Transplants (ATG-perfusion)

Reduction of Ischemic-reperfusion Injury by Ex-vivo ATG-perfusion of Kidneys and Livers Prior Organ Transplantation

The increasing demand for organ transplantation and the shortage of available organs limit the success of organ transplantation programs. Consequently, acceptance of expanded criteria donor (ECD) organs with the consequences of higher risk of unfavorable transplantation outcome has become an increasing reality. Among the most prominent characteristics distinguishing ECD from Standard Criteria Donors (SCD) are risk factors including brain death (BD) or prolonged cold ischemia time (CI) amplifying ischemia reperfusion injury (IRI). Currently there are no standard regimens to improve the quality of ECD organs. Therefore, donor organ treatment might be a promising approach to substantially improve organ quality. It will be investigated whether the application of the peri-operative perfusion of kidneys and livers with the polyclonal antibody rabbit antithymocyte globulin (rATG) ameliorates IRI.

This trial is designed as a parallel armed randomized controlled trial.

Study Overview

• Status: Completed
• Conditions: Organ Preservation Solutions
• Intervention / Treatment: Biological: organ perfusion with rabbit anti-thymocyte globulin (rATG); Other: organ perfusion with saline

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients receiving a kidney or liver transplant from deceased donors

Exclusion Criteria:

• Hepatitis C Virus/Human Immunodeficiency Virus, undergoing re-transplantation or under a public guardian

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AP-KTx/LTx; Transplant recipients receiving an rATG-perfused kidney or liver	Biological: organ perfusion with rabbit anti-thymocyte globulin (rATG)
Placebo Comparator: CP-KTx/LTx; Transplant recipients receiving a control-perfused kidney or liver.	Other: organ perfusion with saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft function	Graft function from baseline defined as serum creatinine (KTx arm) and aspartate transaminase (LTx arm).	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft function - creatinine	Graft function from baseline defined as serum creatinine (mg/dL) for the KTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - glomeralur filtration rate	Graft function from baseline defined as glomerular filtration rate (ml/min/1.73M2) for the KTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - serum urea	Graft function from baseline defined as serum urea (mg/dL) for the KTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - aspartate transaminase	Graft function from baseline defined as aspartate transaminase (mg/dL) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - alanine transaminase	Graft function from baseline defined as alanine transaminase (mg/dL) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - total serum bilirubin	Graft function from baseline defined as total serum bilirubin (mg/dL) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - gamma-glutamyl transpeptidase	Graft function from baseline defined as gamma-glutamyl transpeptidase (mg/dL) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - alkaline phosphatase	Graft function from baseline defined as alkaline phosphatase (mg/dL) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Graft function - quick value	Graft function from baseline defined as quick value (%) for LTx arm.	Days 1-7 post transplantation, month 3, month 6, month 12
Patient age - recipient	Recipient age (years).	Day zero, at the time point of transplantation
Patient age - donor	Donor age (years).	Day zero, at the time point of transplantation
BMI - recipient	Recipient BMI (weight (lb) / [height (in)]2 x 703).	Day zero, at the time point of transplantation
BMI - donor	Donor BMI (weight (lb) / [height (in)]2 x 703).	Day zero, at the time point of transplantation
Sex - recipient	Recipient sex.	Day zero, at the time point of transplantation
Sex - donor	Donor sex.	Day zero, at the time point of transplantation
Cold ischemia time	Cold ischemia time (hours) from cross-clamping until start of anastomosis.	during transplantation
Warm ischemia time	Warm ischemia time (hours) is the time from start of anastomosis until reperfusion.	during transplantation
Panel-reactive antibodies	Presence of panel-reactive antibodies (%) in KTx recipients.	Day zero, at the time point of transplantation
Hospital stay	Hospital stay (days) after transplantation	after transplantation
ICU stay	Intensive care unit stay (days) after transplantation	after transplantation
Mortality	Death rate in the investigated groups.	up to 12 month
Graft loss	Graft loss rate in the investigated groups.	up to 12 month
HLA missmatch	Human leukocyte antigen mismatches in KTx recipients.	Day zero, at the time point of transplantation
Delayed graft function	Development of delayed graft function (requirement of dialysis within the first 7 post operative days) in KTx recipients.	after transplantation
Experimental analysis of perioperative taken biopsies	mRNA Expression of pro-inflammatory and anti-inflammatory cytokine/chemokine pattern in biopsies will be analysed to evaluate immunactivation of the organ	Peri-operatively (zero hour biopsy)
Experimental analysis of peripheral blood monunuclear cells	Leukocyte-composition and activation pattern will be analysed from peripheral blood via flow cytometry of the recipient and the donor	prior transplantation, days 1-7 post transplantation, month 3, month 6, month 12 for lymphocyte expression analysis of peripheral blood

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Publications and helpful links

General Publications

• Ritschl PV, Gunther J, Hofhansel L, Kuhl AA, Sattler A, Ernst S, Friedersdorff F, Ebner S, Weiss S, Bosmuller C, Weissenbacher A, Oberhuber R, Cardini B, Ollinger R, Schneeberger S, Biebl M, Denecke C, Margreiter C, Resch T, Aigner F, Maglione M, Pratschke J, Kotsch K. Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial. Front Immunol. 2018 Aug 24;9:1911. doi: 10.3389/fimmu.2018.01911. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2012
• Primary Completion (Actual): March 4, 2015
• Study Completion (Actual): February 24, 2016

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: UN4640

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No