Low Dose Thymoglobulin to Protect Kidney Function After Liver Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00970073
First received: August 31, 2009
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Liver Transplantation
Biological: Thymoglobulin
Drug: Mycophenolate mofetil
Drug: tacrolimus

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized Controlled Clinical Trial of Low Dose Thymoglobulin and Extended Delay of Calcineurin Inhibitor Therapy for Renal Protection After Liver Transplantation

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Reduced incidence of perioperative acute kidney injury in patients undergoing liver transplant as evidenced by kidney function measurement [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patient survival [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: No ]
  • Graft survival [ Time Frame: 12 months post transplant ] [ Designated as safety issue: No ]
  • Allograft rejection rates at 30 days, 6 and 12 months as proven by biopsy [ Time Frame: 30 days, 6 months, 12 months ] [ Designated as safety issue: Yes ]
  • Renal function measured by eGFR [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: August 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Delayed CNI Group 1
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.
Biological: Thymoglobulin
1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)
Drug: Mycophenolate mofetil
1000 mg PO/IV BID for up to 6 months
Other Name: CellCept
Drug: tacrolimus
Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180
Other Name: Prograf
Experimental: Delayed CNI Group 2
4.5 total mg/kg of Thymoglobulin plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.
Biological: Thymoglobulin
1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)
Drug: Mycophenolate mofetil
1000 mg PO/IV BID for up to 6 months
Other Name: CellCept
Drug: tacrolimus
Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180
Other Name: Prograf
Active Comparator: Early CNI / Control Arm
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).
Drug: Mycophenolate mofetil
1000 mg PO/IV BID for up to 6 months
Other Name: CellCept
Drug: tacrolimus
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.
Other Name: Prograf

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970073

Locations
United States, Ohio
Cleveland Clinic (Main Campus)
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Bijan Eghtesad, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00970073     History of Changes
Other Study ID Numbers: CCIRB 09-432
Study First Received: August 31, 2009
Last Updated: July 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:
calcineurin inhibitor delay
Kidney

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014