Calcineurin Inhibitor Sparing After Kidney Transplantation

Phase 1

Completed

• Conditions: CNI Side Effects
• Interventions: Drug: Rapamune and Cellcept; Drug: Cyclosporine & Cellcept; Drug: Prograf & Cellcept; Drug: Low Dose CNI (Cyclosporine or FK) and Cellcept

• Registration Number: NCT01062555
• Lead Sponsor: University of Minnesota

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-10-01
• Study First Submitted: 2010-02-03
• Study First Submitted QC: 2010-02-03
• Study First Posted: 2010-02-04
• Primary Completion: 2014-04-03
• Study Completion: 2014-04-03
• Results First Submitted: 2020-01-15
• Status Verified: 2020-11
• Results First Submitted QC: 2020-11-17
• Last Update Submitted: 2020-11-17
• Results First Posted: 2020-12-14
• Last Update Posted: 2020-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 527

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase II Arm 2	Rapamune and Cellcept	Rapa and MMF
Phase I Arm 1	Cyclosporine & Cellcept	CSA and MMF
Phase I Arm 2	Prograf & Cellcept	FK and MMF
Phase II Arm 1	Low Dose CNI (Cyclosporine or FK) and Cellcept	Low CNI and MMF

Primary Outcome Measures

Name	Time	Method
Phase I: The Minimization of Negative Side Effects - Patient Survival	6 months	The percentage of patients alive at 6 month post transplant.
Phase I: The Minimization of Negative Side Effects - Graft Survival	6 months	Percent of participants at 6 months with a functioning graft (without graft failure).
Phase II: The Minimization of Negative Side Effects - Graft Survival	up to 7 years	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.
Phase II: Acute Rejection-Free Survival	up to 7 years	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.
Phase II: The Minimization of Negative Side Effects - Patient Survival	up to 7 years	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.
Phase I: Acute Rejection-Free Survival	6 months	Percent of participants at 6 months without acute rejection.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States