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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00170053
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : July 31, 2012
Wyeth is now a wholly owned subsidiary of Pfizer
Genzyme, a Sanofi Company
Raymond Heilman
Information provided by:
Mayo Clinic

Brief 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.

Condition or disease Intervention/treatment Phase
Kidney Diseases Drug: Sirolimus Phase 1

Detailed Description:


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 177 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2005
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Intervention Details:
  • 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.

Primary Outcome Measures :
  1. Renal function [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Renal function [ Time Frame: 2 years ]
  2. Transplant biopsy histology [ Time Frame: 2 years ]
  3. Patient and graft survival [ Time Frame: 2years ]
  4. Acute rejection rate [ Time Frame: 1 month ]
  5. Number of patients steroid free [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00170053

United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
Sponsors and Collaborators
Mayo Clinic
Wyeth is now a wholly owned subsidiary of Pfizer
Genzyme, a Sanofi Company
Raymond Heilman
Principal Investigator: Thomas A. Gonwa, M.D. Mayo Clinic

Responsible Party: Thomas A. Gonwa, MD, Mayo Clinic Identifier: NCT00170053     History of Changes
Other Study ID Numbers: 37-05
Wyeth 0468H-101898
First Posted: September 15, 2005    Key Record Dates
Last Update Posted: July 31, 2012
Last Verified: July 2012

Keywords provided by Mayo Clinic:
Kidney Transplantation

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Antibiotics, Antitubercular
Antitubercular Agents