Comparison of Standard Versus Low Dose Advagraf® With or Without Angiotensin-converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) on Histology and Function of Renal Allografts

A Comparison of Effects of Standard Dose vs. Low Dose Advagraf® With IL-2 Receptor Antibody Induction, MMF and Steroids, With or Without ACEi/ARB - Based Antihypertensive Therapy on Renal Allograft Histology, Function, and Immune Response

This is a multicentre study examining the use of Advagraf-minimization strategy and/or the use of an inhibitor of the renin-angiotensin system in reducing chronic rejection in renal allografts.

The study will consist of the following 4 treatment groups.:

1. Standard dose Advagraf with angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) antihypertensive therapy
2. Standard dose Advagraf without ACEi/ARB antihypertensive therapy
3. Low dose Advagraf with ACEi/ARB antihypertensive therapy
4. Low dose Advagraf without ACEi/ARB antihypertensive therapy

Inclusion Criteria:

• Subject is the recipient of a first or second deceased or living donor renal transplant (one kidney only)
• Subject must have at least one HLA-mismatch with the donor. HLA identical donor-recipient pairs are not eligible
• Subject understands either English or French
• If female and of child-bearing potential, subject has a negative pregnancy test and utilizes adequate contraceptive methods

Exclusion Criteria:

• Presence of donor specific antibody
• Subject who is currently participating in a study with investigational drug, or who has received investigational drug within three months prior to randomization. Observational studies are acceptable
• Subject who has lost a previous graft for immunological reasons less than one year from transplant
• Subject is pregnant or breastfeeding
• Subject receives a kidney lacking pre-implantation biopsy
• Subject has significant disease (e.g. malignancy or uncontrolled infection) or disability (e.g. cognitive defect) which prevents understanding of, or adherence to the protocol
• Subject who in the opinion of the Investigator, require ACEi/ARB therapy post-transplant for any indication
• Subject who requires induction with Thymoglobulin, Campath, antithymocyte globulin (ATG), antilymphocyte globulin (ALG) or any biological induction agent other than basiliximab. Unplanned post-transplant use of these prohibited drugs for clinical indications post-transplant is allowed
• Subject has plans to become pregnant within 2 years post-transplant
• Subject who has a positive T-cell or B-cell crossmatch. Subjects with a weakly positive B-cell cross-match that tests negative following DTT reduction are acceptable
• Subject who has a requirement for maintenance immunosuppressant therapy with the exception of low dose steroid or mycophenolate mofetil (MMF). A subject who is on low dose tacrolimus maintenance therapy will be eligible provided the tacrolimus is withheld at least 1 week prior to transplant