Low Dose Thymoglobulin to Protect Kidney Function After Liver Transplant

NCT ID: NCT00970073

Last Updated: 2018-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2015-12-31

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.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Delayed CNI Group 1

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)

Group Type: EXPERIMENTAL

Thymoglobulin 3mg total

Intervention Type: BIOLOGICAL

1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)

Mycophenolate mofetil

Intervention Type: DRUG

1000 mg PO/IV BID for up to 6 months

tacrolimus 3-8

Intervention Type: DRUG

Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180

Delayed CNI Group 2

Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration)

Group Type: EXPERIMENTAL

Thymoglobulin 4.5mg total

Intervention Type: BIOLOGICAL

1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)

Mycophenolate mofetil

Intervention Type: DRUG

1000 mg PO/IV BID for up to 6 months

tacrolimus 3-8

Intervention Type: DRUG

Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180

Early CNI / Control Arm

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).

Group Type: ACTIVE_COMPARATOR

Mycophenolate mofetil

Intervention Type: DRUG

1000 mg PO/IV BID for up to 6 months

tacrolimus 8-12

Intervention Type: DRUG

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.

Interventions

Thymoglobulin 3mg total

1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)

Intervention Type: BIOLOGICAL

Thymoglobulin 4.5mg total

1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)

Intervention Type: BIOLOGICAL

Mycophenolate mofetil

1000 mg PO/IV BID for up to 6 months

Intervention Type: DRUG

tacrolimus 3-8

Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180

Intervention Type: DRUG

tacrolimus 8-12

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.

Intervention Type: DRUG

Other Intervention Names

CellCept; Prograf; Prograf

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Bijan Eghtesad, MD

HPBT Staff Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bijan Eghtesad, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic (Main Campus)

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CCIRB 09-432

Identifier Type: -

Identifier Source: org_study_id