Comparison of Sirolimus to Tacrolimus for Long Term Therapy in Kidney Transplant With no Steroids

Kidney Diseases Clinical Trial

Official title:

Randomized Trial of Thymoglobulin Induction, Initial Tacrolimus, and Mycophenolate Mofetil Therapy With Steroid Avoidance in Primary Kidney Transplant Recipients Followed by Continued Tacrolimus/Mycophenolate Mofetil Therapy vs. Sirolimus/ Mycophenolate Mofetil Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00170053
• Other study ID #: 37-05
• Secondary ID: Wyeth 0468H-1018
• Status: Completed
• Phase: Phase 1
• First received: September 12, 2005
• Last updated: July 27, 2012
• Start date: June 2005
• Est. completion date: September 2008

Study information

• Verified date: July 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Kidney transplant patients will be treated with Thymoglobulin (5 days), tacrolimus (Prograf), and mycophenolate mofetil (Cellcept) from the time of transplant. They will only receive steroids for 4 days and no prednisone after that. At 1 month, they will have a kidney biopsy and if it is ok, patients will be treated long term with either continued tacrolimus/mycophenolate mofetil or be switched to sirolimus (Rapamune)/mycophenolate mofetil. This will be done randomly in a manner similar to flipping a coin. The investigators are trying to determine if after the initial therapy patients can stay off steroids long term and get better kidney function if they are treated with sirolimus compared to tacrolimus. Patients will be followed for 3 years and will repeat kidney biopsies at 1 and 2 years after transplant.

Description:

Abstract:

Corticosteroids have been a mainstay of immunosuppression for kidney transplantation, but they are associated with significant toxicity after long-term use. Recent studies have concluded that steroid avoidance is safe and effective when combined with modern immunosuppressive maintenance therapy in low risk kidney transplant recipients. These studies have included antilymphocyte induction therapy with either an anti IL-2 receptor antibody, or an antithymocyte globulin, such as rabbit polyclonal antithymocyte globulin (Thymoglobulin). Mayo Clinic Scottsdale has adopted Thymoglobulin induction, tacrolimus, and mycophenolate mofetil with rapid steroid taper as their standard immunosuppressive therapy in low risk patients. Mayo Clinic Jacksonville is also utilizing this protocol. Together, both sites have utilized this approach in 64 patients. Recent improvements in immunosuppressive regimens have decreased acute rejection in kidney transplant recipients and increased one-year graft survival to nearly 90%. However, long-term graft survival has changed little with 30% of grafts being lost to ''chronic allograft nephropathy'' (CAN) in the first five years after transplantation. A recent paper highlighted this dilemma and demonstrated that a major cause of late CAN was chronic exposure to the nephrotoxic effects of calcineurin inhibitors (CNI) tacrolimus and cyclosporine and possibly cytomegalovirus infection. In this study, we will focus on the role of CNI in CAN. We propose a prospective, randomized, non-blinded trial of Thymoglobulin induction with rapid steroid elimination accompanied by tacrolimus (TAC) and mycophenolate mofetil (MMF) maintenance therapy. Patients are to be randomized at 1 month post-operatively to either remain on TAC/MMF or switch to SRL/MMF. The primary endpoint will be renal function at 1-year post-transplant. Secondary endpoints will include renal function at 2 years post-transplant, histology seen on protocol biopsies at 1 and 2 years post-transplant, incidence of biopsy proven rejection at 12 months, patient survival, graft survival, proportion of patients steroid free at 12 months, infectious complications, bone mineral density analysis, incidence of hyperlipidemia, and the incidence of new onset post-transplant diabetes mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Primary deceased or living donor renal transplant recipients

2. Re-transplant recipients for which the first kidney transplant was lost for technical reasons with no sensitization (panel-reactive antibody [PRA] < 20%) or 1st lost due to recurrent disease, that is not steroid responsive.

3. Age > 18

4. Negative pregnancy test if female and of childbearing age. In addition, females of childbearing age must agree to use effective contraception for the duration of the study.

5. Patient must sign informed consent prior to transplant.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Diseases

Intervention

Drug:
• Sirolimus
10 mg oral loading dose followed by 5 mg/day. Measure Sirolimus level weekly and adjust to level of 10-15 ng/ml.

Locations

Country	Name	City	State
United States	Mayo Clinic	Jacksonville	Florida

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	Genzyme, a Sanofi Company, Raymond Heilman, Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal function		1 year	No
Secondary	Renal function		2 years	No
Secondary	Transplant biopsy histology		2 years	No
Secondary	Patient and graft survival		2years	No
Secondary	Acute rejection rate		1 month	No
Secondary	Number of patients steroid free		1 year	No