Antibody and Delayed Cyclosporine Versus Initial Cyclosporine Alone in Patients Receiving Kidney Transplants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00007787
First received: January 4, 2001
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to see if kidney function can be improved during transplants by giving the drug Thymoglobulin with delayed cyclosporine treatment instead of initial cyclosporine treatment.

There have been improvements for patients receiving kidney transplants, yet acute rejection is still a problem. This can lead to kidney failure over time. Patients whose graft fails to function properly in the first week after transplant do not do as well after 5 years as compared to patients without early problems. This study will see if Thymoglobulin, a drug that suppresses the immune system, will improve early graft function.


Condition Intervention
Kidney Transplantation
Chronic Allograft Nephropathy
Biological: Cyclosporine
Biological: Anti-human thymocyte globulin (rabbit)
Drug: Tacrolimus

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Antibody Plus Delayed CSA vs CSA in Determining Delayed Graft Function in Cadaver Transplant Recipients

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Graft function measurnment [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    measured by a calculated creatinine clearance. Creatinine Clearance for males will be computed using the following: [weight in kg * (140 - age in years)]/ [72 * serum creatinine mg/dl]. For females, eighty-five percent of this value will be used.


Estimated Enrollment: 350
Study Start Date: April 2000
Study Completion Date: March 2004
Arms Assigned Interventions
Experimental: Antibody plus delayed cyclosporine therapy
Anti-human thymocyte globulin (rabbit) (Thymoglobulin®) is admistred at the time of transplant followed delayed clyclosporine A therapy post tranplant.
Biological: Cyclosporine Biological: Anti-human thymocyte globulin (rabbit)
Anti-human thymocyte globulin (rabbit) will be given at a dose of 1.5 mg/kg while undergoing transplantation. Second and subsequent doses of Thymoglobulin® will be administered if, at 24 hours post-anastomosis, the serum creatinine has not decreased by at least 20% from the pre-transplant level. Additional Anti-human thymocyte globulin (rabbit) will be given at a dose of 1.5mg/kg daily for a minimum of 5 days to a maximum of 7 days.
Other Name: Thymoglobulin®
Drug: Tacrolimus
Active Comparator: Standard cyclosporine A therapy
Cyclosporine A therapy (either Cyclosporine or Tacrolimus) will be initiated pre-transplantations
Biological: Cyclosporine Drug: Tacrolimus

Detailed Description:

While graft survival of post renal transplant has improved over the last decades, acute rejection remains a problem that clinical research has sought to minimize through improved strategies. Graft survival prognosis is significantly worsened in patients whose allografts exhibit delayed function and patients may require early dialysis. Data shows that cadaveric organ recipients requiring dialysis use in the first transplant week have a 5-year post-graft survival rate of 51 percent compared to 70 percent for those free of this complication. A recent evaluation of Thymoglobulin (a rabbit-derived polyclonal antibody; an immunosuppressant) suggests it is an effective agent worthy of further evaluation as induction therapy. This trial evaluates whether a decreased DGF is seen with an improved Day 90 graft function.

Recipients of a first or second cadaver kidney transplant are randomized pre-transplant to 1 of 2 treatment groups. One group receives antibody therapy (Thymoglobulin) at the time of transplant and delayed cyclosporine therapy. The other group starts cyclosporine therapy at the time of transplant without Thymoglobulin. DGF is diagnosed by a less than 20 percent decrease in the serum creatinine levels in the first 24 hours post-transplant and/or the need for dialysis. Patients on the antibody arm receive additional antibody if they experience DGF. Biopsies are performed in all cases of suspected rejection and any patient with biopsy-confirmed acute cellular rejection receives treatment. Patients have regular examinations including blood tests and are evaluated for kidney function and incidence of complications for 24 months after the transplant. The trial endpoint of graft function encompasses graft survival and graft function as calculated by creatinine clearance.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are receiving a first or second kidney transplant.
  • Are at least 21 years old.
  • Understand the purposes and risks of the study and have given consent.
  • Agree to use an acceptable form of birth control for a year following transplant.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have received a kidney transplant from a living donor.
  • Have had multiple organ transplants.
  • Are allergic to Thymoglobulin (contains a rabbit protein).
  • Are pregnant.
  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: NCT00007787

Locations
United States, Maryland
Ilene Blechman-Krom
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
Investigators
Study Chair: Arthur Matas, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00007787     History of Changes
Other Study ID Numbers: DAIT DG01
Study First Received: January 4, 2001
Last Updated: January 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Antibodies
Tacrolimus
Cyclosporins
Cyclosporine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 19, 2014