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

NCT ID: NCT00170053

Last Updated: 2012-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

177 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2008-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Kidney Diseases

Keywords

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Kidney Transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Sirolimus

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wyeth is now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

Raymond Heilman

UNKNOWN

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Mayo Clinic

Principal Investigators

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Thomas A. Gonwa, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Jacksonville, Florida, United States

Site Status

Countries

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United States

Other Identifiers

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Wyeth 0468H-101898

Identifier Type: -

Identifier Source: secondary_id

37-05

Identifier Type: -

Identifier Source: org_study_id