Calcineurin Inhibitor Sparing After Kidney Transplantation (CNI-Sparing)

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

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.

Study Overview

• Status: Completed
• Conditions: CNI Side Effects
• Intervention / Treatment: Drug: Cyclosporine & Cellcept; Drug: Prograf & Cellcept; Drug: Low Dose CNI (Cyclosporine or FK) and Cellcept; Drug: Rapamune and Cellcept

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 Type: Interventional
• Enrollment (Actual): 527
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phase I Arm 1; CSA and MMF	Drug: Cyclosporine & Cellcept; 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.; Other Names: CSA, Gengraf, Neoral, Sandimmune, MMF, Mycophenolate Mofetil
Active Comparator: Phase I Arm 2; FK and MMF	Drug: Prograf & Cellcept; 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.; Other Names: FK, Tacrolimus, MMF, Mycophenolate Mofetil
Active Comparator: Phase II Arm 1; Low CNI and MMF	Drug: Low Dose CNI (Cyclosporine or FK) and Cellcept; 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.; Other Names: Gengraf, Neoral, Sandimmune, Tacrolimus, Prograf, MMF
Active Comparator: Phase II Arm 2; Rapa and MMF	Drug: Rapamune and Cellcept; 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.; Other Names: Sirolimus, MMF, Mycophenolate Mofetil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer; Roche Pharma AG; Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2006
• Primary Completion (Actual): April 3, 2014
• Study Completion (Actual): April 3, 2014

Study Registration Dates

• First Submitted: February 3, 2010
• First Submitted That Met QC Criteria: February 3, 2010
• First Posted (Estimate): February 4, 2010

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Sirolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 0604M85327