Calcineurin Inhibitor Sparing After Kidney Transplantation

Study Overview
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Brief Summary
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Reducing drug side effects is a key issue in transplantation. One class of drugs commonly used, calcineurin inhibitors (CNIs), is associated with negative side effects, namely, toxicity to the transplanted kidney. In some patients, this toxicity is thought to be associated with loss of transplant function in those who have had their transplants for many years. The introduction of new immunosuppression medications however, has provided the opportunity to minimize or avoid CNIs, which may reduce the occurrence of toxicity to the kidney.

Detailed Description
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It is clear that minimizing the use of CNIs may be beneficial to some or all kidney transplant recipients. The purpose of this study is to determine whether minimization of these CNI drugs will improve patient survival rates and long-term kidney function. If the subject agrees to participate in this research project, they will be randomly assigned to one of two different immunosuppression drug combinations. All of the drugs used in this study are standard FDA Approved immunosuppressive drugs currently in use by transplant patients. It is unclear however, which combination provides a better long-term outcome. If after six months of being on the study the subject has not experienced a rejection episode that excludes them from participating in the second phase of this study, they will asked whether or not they would like to continue the study. If they decide to participate in Phase II, there will be another randomization to one of two different immunosuppression drug combinations. This will involve either being assigned to a group that will have their CNI dose lowered or a group that will have their CNI drug stopped and replaced with a non-CNI drug called Sirolimus. Phase II begins at 6 months post-transplant and a second consent will be obtained for those who participate in Phase II.

Official Title
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Calcineurin-Sparing in a Steroid-free Maintenance Immunosuppression Protocol After Kidney Transplantation

Conditions
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CNI Side Effects

Intervention / Treatment
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* Drug: Cyclosporine & Cellcept
* Drug: Prograf & Cellcept
* Drug: Low Dose CNI (Cyclosporine or FK) and Cellcept
* Drug: Rapamune and Cellcept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney Transplant Recipients > 18 years old First or Second Kidney Transplant only Exclusion Criteria: Kidney Transplant Recipients < 18 years old Kidney Transplant Recipients who have a history of > 2 kidney transplants Kidney Transplant Recipients with an already functioning non-renal transplant Kidney Transplant Recipients who receive another organ simultaneously at the same time of their kidney transplant (example: Kidney/pancreas, kidney/liver) Non-skin malignancy with 2 years previous to enrollment Donor Specific Antibodies to kidney donor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phase I Arm 1<br>CSA and MMF | Drug: Cyclosporine & Cellcept<br>* Dose and frequency determined as usual by transplant physicians. The drugs are not experimental drugs. The study is looking at reducing negative side effects of some of the drugs.<br>* Other names: CSA, Gengraf, Neoral, Sandimmune, MMF, Mycophenolate Mofetil;|
| Active Comparator: Phase I Arm 2<br>FK and MMF | Drug: Prograf & Cellcept<br>* Dose and frequency determined as usual by transplant physicians. The drugs are not experimental drugs. The study is looking at reducing negative side effects of some of the drugs.<br>* Other names: FK, Tacrolimus, MMF, Mycophenolate Mofetil;|
| Active Comparator: Phase II Arm 1<br>Low CNI and MMF | Drug: Low Dose CNI (Cyclosporine or FK) and Cellcept<br>* Dose and frequency determined as usual by transplant physicians. The drugs are not experimental drugs. The study is looking at reducing negative side effects of some of the drugs.<br>* Other names: Gengraf, Neoral, Sandimmune, Tacrolimus, Prograf, MMF;|
| Active Comparator: Phase II Arm 2<br>Rapa and MMF | Drug: Rapamune and Cellcept<br>* Dose and frequency determined as usual by transplant physicians. The drugs are not experimental drugs. The study is looking at reducing negative side effects of some of the drugs.<br>* Other names: Sirolimus, MMF, Mycophenolate Mofetil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: The Minimization of Negative Side Effects - Patient Survival | The percentage of patients alive at 6 month post transplant. | 6 months | 
| Phase II: The Minimization of Negative Side Effects - Patient Survival | The percentage of patients alive at 7 years post transplant or at the end of study activities. Not all participants completed 7-year follow-up. | up to 7 years | 
| Phase I: The Minimization of Negative Side Effects - Graft Survival | Percent of participants at 6 months with a functioning graft (without graft failure). | 6 months | 
| Phase II: The Minimization of Negative Side Effects - Graft Survival | The percentage of patients with a functioning graft (without graft failure) at 7 years post transplant or at the end of study activities. Not all participants completed 7-year follow-up. | up to 7 years | 
| Phase I: Acute Rejection-Free Survival | Percent of participants at 6 months without acute rejection. | 6 months | 
| Phase II: Acute Rejection-Free Survival | The percentage of patients without acute rejection at 7 years post transplant or at the end of study activities. Not all participants completed 7-year follow-up. | up to 7 years |