Overview

This trial is active, not recruiting.

Condition liver transplantation
Treatments thymoglobulin, mycophenolate mofetil, tacrolimus
Sponsor The Cleveland Clinic
Collaborator Genzyme, a Sanofi Company
Start date August 2009
End date December 2013
Trial size 30 participants
Trial identifier NCT00970073, CCIRB 09-432

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose prevention
Arm
(Experimental)
3 mg/kg total Thymoglobulin administered on Days 0 and 2 (after transplant), plus MMF and corticosteroids. CNI administration delayed until 10 days post transplant.
thymoglobulin
1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)
mycophenolate mofetil CellCept
1000 mg PO/IV BID for up to 6 months
tacrolimus Prograf
Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180
(Experimental)
4.5 total mg/kg of Thymoglobulin plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.
thymoglobulin
1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)
mycophenolate mofetil CellCept
1000 mg PO/IV BID for up to 6 months
tacrolimus Prograf
Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180
(Active Comparator)
Standard post liver transplant therapy to include: Calcineurin inhibitor (CNI) initiated within 48 hours post-transplant, plus mycophenolate mofetil (MMF) and corticosteroids to be administered within 24 hours after transplant (Day 0).
mycophenolate mofetil CellCept
1000 mg PO/IV BID for up to 6 months
tacrolimus Prograf
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.

Primary Outcomes

Measure
Reduced incidence of perioperative acute kidney injury in patients undergoing liver transplant as evidenced by kidney function measurement
time frame: 30 days

Secondary Outcomes

Measure
Patient survival
time frame: 12 months post-transplant
Graft survival
time frame: 12 months post transplant
Allograft rejection rates at 30 days, 6 and 12 months as proven by biopsy
time frame: 30 days, 6 months, 12 months
Renal function measured by eGFR
time frame: 12 months post-transplant

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

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

Additional Information

Official title A Randomized Controlled Clinical Trial of Low Dose Thymoglobulin and Extended Delay of Calcineurin Inhibitor Therapy for Renal Protection After Liver Transplantation
Principal investigator Bijan Eghtesad, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2013.
Information provided to ClinicalTrials.gov by The Cleveland Clinic.