Low Dose Thymoglobulin to Protect Kidney Function After Liver Transplant

Study Overview
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Brief Summary
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This study will evaluate the use of a drug called Thymoglobulin, combined with a delayed start of the anti-rejection drugs (10 days after liver transplant), compared to the current approach of starting anti-rejection drugs called calcineurin inhibitors or CNI's within 2 days after the liver transplant.

Detailed Description
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Strong anti-rejection drugs like tacrolimus or cyclosporine, are given to patients who have received transplants, to ensure that the patient's body does not reject the new organ. In some cases, while anti-rejection medications protect a newly transplanted liver, they can injure the patient's kidneys and cause them not to work as well as they should. The purpose of this pilot study is to determine the best way to protect kidney function and to ensure that the newly transplanted liver is not rejected. This study will evaluate the use of a drug called Thymoglobulin, combined with a delayed start of the anti-rejection drugs (10 days after liver transplant), compared to the current approach of starting anti-rejection drugs called calcineurin inhibitors or CNI's within 2 days after the liver transplant.

Official Title
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A Randomized Controlled Clinical Trial of Low Dose Thymoglobulin and Extended Delay of Calcineurin Inhibitor Therapy for Renal Protection After Liver Transplantation

Conditions
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Liver Transplantation

Intervention / Treatment
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* Biological: Thymoglobulin 3mg total
* Biological: Thymoglobulin 4.5mg total
* Drug: Mycophenolate mofetil
* Drug: tacrolimus 3-8
* Drug: tacrolimus 8-12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing deceased donor solitary liver transplantation Adults aged 18-70 at time of transplantation Hepatocellular carcinoma as indication for OLT within the Milan Criteria Hepatitis C positive or negative patients Willingness to comply with study procedures Able to sign informed consent Exclusion Criteria: Prior kidney transplantation Congenital or iatrogenic absence of one kidney Subjects on renal replacement therapy at the time of OLT MELD score > 28 HIV positive patient Patient with current severe systemic infection History of bacterial peritonitis within 30 days prior to OLT Active infection or recent infection within 30 days prior to OLT Use of calcineurin inhibitor continuously for more than 90 days within the past 6 months History of hypersensitivity to thymoglobulin, rabbits, tacrolimus or iohexol Women of childbearing age who are unwilling to use effective contraceptive methods during the duration of the study

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delayed CNI Group 1<br>Thymoglobulin 3mg total, administered on Days 0 and 2 (after transplant), plus MMF and corticosteroids. CNI administration delayed until 10 days post transplant. tacrolimus 3-8 (trough concentration) | Biological: Thymoglobulin 3mg total<br>* 1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)<br>Drug: Mycophenolate mofetil<br>* 1000 mg PO/IV BID for up to 6 months<br>* Other names: CellCept;Drug: tacrolimus 3-8<br>* Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180<br>* Other names: Prograf;|
| Experimental: Delayed CNI Group 2<br>Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration) | Biological: Thymoglobulin 4.5mg total<br>* 1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)<br>Drug: Mycophenolate mofetil<br>* 1000 mg PO/IV BID for up to 6 months<br>* Other names: CellCept;Drug: tacrolimus 3-8<br>* Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180<br>* Other names: Prograf;|
| Active Comparator: Early CNI / Control Arm<br>Standard post liver transplant therapy to include: tacrolimus 8-12 (trough concentration) initiated within 48 hours post-transplant, plus mycophenolate mofetil (MMF) and corticosteroids to be administered within 24 hours after transplant (Day 0). | Drug: Mycophenolate mofetil<br>* 1000 mg PO/IV BID for up to 6 months<br>* Other names: CellCept;Drug: tacrolimus 8-12<br>* Trough concentration between 8 ng/mL and 12 ng/mL on Days 0-10; between 6 ng/mL and 12 ng/mL on Days 10-30; between 6 ng/mL and 10 ng/mL Days 31-60; between 5 ng/mL and 8 ng/mL Days 61-179; and between 3 ng/mL and 8 ng/mL beyond Day 180.<br>* Other names: Prograf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery | Postoperative acute kidney injury is measured as reduced (eGFR) within 12 months post-surgery. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Survival |  | 12 months post-transplant | 
| Graft Survival | 90% graft survival, related to the deaths of 3 patients during the study period. | 12 months post transplant | 
| Allograft Rejection Rates at 30 Days | Acute Allograft Rejection | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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calcineurin inhibitor delay, Kidney