Overview

This trial is active, not recruiting.

Conditions end-stage renal disease, renal transplantation
Treatments rabbit anti-thymocyte globulin (ratg), mycophenolate mofetil, rabbit anti-thymocyte globulin, kidney transplantation, sirolimus, tacrolimus
Target mTOR
Sponsor University of Nebraska
Collaborator Genzyme, a Sanofi Company
Start date April 2004
End date April 2011
Trial size 180 participants
Trial identifier NCT00556933, 286-03

Summary

This study evaluates two potential improvements to the standard immunosuppression regimen used at the investigators' institution to prevent rejection of transplanted kidneys. These two potential improvements are each applied in sequence to half of the study patients, creating 4 study arms; the other half receive the standard treatment. The two potential improvements are:

1. Administering the immunosuppression induction agent rATG ("rabbit anti-thymocyte globulin") in a single dose at the time of transplantation, instead of in the usual series of 4 smaller doses over 6 days.

2. After 6 months, modifying the maintenance immunosuppression used to prevent rejection by replacing the drug tacrolimus with mycophenolate mofetil (MMF).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Kidney transplant recipients given a single large dose of rATG and maintained on tacrolimus and sirolimus for chronic immunosuppression.
rabbit anti-thymocyte globulin (ratg) Thymoglobulin
A single 6 mg/kg dose of rATG administered intravenously over 24 hours, beginning before kidney transplantation. Administration of the drug is begun as early as practical, usually after general anesthesia has been established but before surgery has started. The rATG is therefore administered for about two hours before blood flow is restored to the kidney undergoing transplantation.
kidney transplantation
Transplantation of an organ-donor kidney into a dialysis-dependent patient with renal failure.
sirolimus Rapamune, rapamycin
Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection
tacrolimus FK506
Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.
(Active Comparator)
Kidney transplant recipients given 4 small doses of rATG and maintained on tacrolimus and sirolimus for chronic immunosuppression.
rabbit anti-thymocyte globulin Thymoglobulin
6 mg/kg rabbit anti-thymocyte globulin delivered in 4 doses of 1.5 mg/kg each, the first administered at the time of kidney transplantation. Subsequent doses are administered on days 2, 4, and 6.
kidney transplantation
Transplantation of an organ-donor kidney into a dialysis-dependent patient with renal failure.
sirolimus Rapamune, rapamycin
Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection
tacrolimus FK506
Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.
(Experimental)
Kidney transplant recipients given a single large dose of rATG and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months.
rabbit anti-thymocyte globulin (ratg) Thymoglobulin
A single 6 mg/kg dose of rATG administered intravenously over 24 hours, beginning before kidney transplantation. Administration of the drug is begun as early as practical, usually after general anesthesia has been established but before surgery has started. The rATG is therefore administered for about two hours before blood flow is restored to the kidney undergoing transplantation.
mycophenolate mofetil CellCept
Patients are switched approximately 6 months after kidney transplantation from maintenance immunosuppression with tacrolimus and sirolimus to maintenance with mycophenolate mofetil and sirolimus. The drug is administered orally, taken daily, with dose adjusted in proportion to measured blood levels, and is required indefinitely to prevent rejection of the transplanted kidney.
kidney transplantation
Transplantation of an organ-donor kidney into a dialysis-dependent patient with renal failure.
sirolimus Rapamune, rapamycin
Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection
tacrolimus FK506
Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.
(Experimental)
Kidney transplant recipients given 4 small doses of rATG and maintained on tacrolimus and sirolimus for chronic immunosuppression until tacrolimus is replaced with mycophenolate mofetil after about 6 months.
mycophenolate mofetil CellCept
Patients are switched approximately 6 months after kidney transplantation from maintenance immunosuppression with tacrolimus and sirolimus to maintenance with mycophenolate mofetil and sirolimus. The drug is administered orally, taken daily, with dose adjusted in proportion to measured blood levels, and is required indefinitely to prevent rejection of the transplanted kidney.
rabbit anti-thymocyte globulin Thymoglobulin
6 mg/kg rabbit anti-thymocyte globulin delivered in 4 doses of 1.5 mg/kg each, the first administered at the time of kidney transplantation. Subsequent doses are administered on days 2, 4, and 6.
kidney transplantation
Transplantation of an organ-donor kidney into a dialysis-dependent patient with renal failure.
sirolimus Rapamune, rapamycin
Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection
tacrolimus FK506
Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.

Primary Outcomes

Measure
Chronic Allograft Nephropathy (cumulative calcineurin-inhibitor nephrotoxicity/transplant nephropathy) per clinically-indicated and protocol surveillance biopsies (Banff grading criteria).
time frame: Two years
Renal function by either measured 24-hour urine creatinine clearance at 1, 3, 6, 12 and 24 months or calculated GFR (Glomerular Filtration Rate) by using the abbreviated MDRD (aMDRD) formula and patient serum creatinine and demographic data.
time frame: Two years

Secondary Outcomes

Measure
Safety profile to consist of CMV disease, opportunistic infections, PTLD, hyperlipidemia, wound healing problems, and lymphoceles
time frame: Two years
Requirement for additional immunosuppression (such as corticosteroids, antimetabolites or other immunosuppressive agents)
time frame: Two years
Acute rejection per kidney biopsy (Banff grading criteria)
time frame: Two years
Acute Tubular Necrosis (ATN) rate, defined as the requirement for dialysis within 7 days post-transplantation.
time frame: Two years
Graft survival
time frame: Two years
Patient survival
time frame: Two years
Immunological parameters, i.e., lymphoid cell sub-type absolute numbers and ratios
time frame: Two years
New-onset BK virus infection per kidney biopsy
time frame: Two years
New-onset diabetes and hyperglycemia after transplantation
time frame: Two years

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Primary renal transplant recipient for end-stage renal disease Exclusion Criteria: - Recipient age < 18 years or > 65 years - Previous history of CMV disease - Hepatitis B and C recipients - Primary disease states that require steroids for immunosuppression - Re-transplant with immunological cause of renal or pancreas loss - Non heart beating donors - Recipient of pediatric en bloc kidneys - Recipient with a PRA > 75% - Patients who have received 3 or more prior transplants, excluding pancreas - Patients who are past recipients of other solid organ transplants - Previous history of BK virus - Previous treatment with Thymoglobulin - Allergy to rabbits - Simultaneous Kidney/Pancreas transplantation

Additional Information

Official title Prospective, Randomized Trial of Thymoglobulin Induction Therapy for Renal Transplantation: Single Versus Alternate Day Administration
Description The two treatment innovations in this study of immunosuppression in kidney transplantation are aimed at making the transplanted kidney function sooner and last longer than is usual with standard immunosuppression regimens, but without increasing the likelihood of rejection. The first innovation, delivering the induction agent rATG in a single large dose rather than as a series of smaller doses over 6-8 days, is expected to produce better graft function right away, possibly by reducing some of the injury to the kidney that accompanies the restoration of blood flow during transplantation ("reperfusion injury"). Some evidence has been developed by investigators elsewhere to suggest this will happen. The second innovation, replacing tacrolimus with MMF after 6 months, is intended to eliminate a well-established major cause of ongoing toxic damage to the kidney. While tacrolimus does a good job of preventing rejection, the cost in continuing toxic injury to the kidney is high, leading inevitably to eventual graft failure, the inability of the transplanted kidney to continue filtering the blood and making adequate volumes of high-quality urine.
Trial information was received from ClinicalTrials.gov and was last updated in January 2010.
Information provided to ClinicalTrials.gov by University of Nebraska.