Low Dose Thymoglobulin to Protect Kidney Function After Liver Transplant

Not Applicable

Completed

• Conditions: Liver Transplantation
• Interventions: Biological: Thymoglobulin 4.5mg total; Biological: Thymoglobulin 3mg total; Drug: tacrolimus 8-12; Drug: Mycophenolate mofetil; Drug: tacrolimus 3-8

• Registration Number: NCT00970073
• Lead Sponsor: The Cleveland Clinic

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-08
• Study First Submitted: 2009-08-31
• Study First Submitted QC: 2009-09-01
• Study First Posted: 2009-09-02
• Primary Completion: 2015-06-15
• Study Completion: 2015-12
• Results First Submitted: 2018-06-12
• Status Verified: 2018-09
• Results First Submitted QC: 2018-09-10
• Last Update Submitted: 2018-09-10
• Results First Posted: 2018-10-09
• Last Update Posted: 2018-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early CNI / Control Arm	tacrolimus 8-12	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).
Delayed CNI Group 2	Thymoglobulin 4.5mg total	Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration)
Delayed CNI Group 1	Thymoglobulin 3mg total	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)
Delayed CNI Group 1	tacrolimus 3-8	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)
Delayed CNI Group 2	tacrolimus 3-8	Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration)
Delayed CNI Group 1	Mycophenolate mofetil	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)
Delayed CNI Group 2	Mycophenolate mofetil	Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration)
Early CNI / Control Arm	Mycophenolate mofetil	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).

Primary Outcome Measures

Name	Time	Method
Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery	12 Months	Postoperative acute kidney injury is measured as reduced (eGFR) within 12 months post-surgery.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cleveland Clinic (Main Campus); 🇺🇸 Cleveland, Ohio, United States