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

Astellas

Status and phase: Completed; Phase 3

Conditions: Kidney Transplantation

Treatments: Drug: Ramipril; Drug: Cellcept; Drug: Irbesartan; Biological: Simulect; Drug: Corticosteroids; Drug: tacrolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00933231

FKC-014

Details and patient eligibility

About

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.

Full description

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

Enrollment: 281 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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281 participants in 4 patient groups

Tacrolimus Standard Dose with ACEi/ARB

Active Comparator group

Description:

Participants receive a standard dose of tacrolimus with ACEi/ARB.

Treatment:

Drug: tacrolimus

Drug: Corticosteroids

Biological: Simulect

Drug: tacrolimus

Drug: Irbesartan

Drug: Cellcept

Drug: Ramipril

Tacrolimus Standard Dose without ACEi/ARB

Active Comparator group

Description:

Participants receive a standard dose of tacrolimus without ACEi/ARB.

Treatment:

Drug: tacrolimus

Drug: Corticosteroids

Biological: Simulect

Drug: tacrolimus

Drug: Cellcept

Tacrolimus Low Dose with ACEi/ARB

Experimental group

Description:

Participants receive a low dose of tacrolimus with ACEi/ARB.

Treatment:

Drug: tacrolimus

Drug: Corticosteroids

Biological: Simulect

Drug: tacrolimus

Drug: Irbesartan

Drug: Cellcept

Drug: Ramipril

Tacrolimus Low Dose without ACEi/ARB

Experimental group

Description:

Participants receive a low dose of tacrolimus without ACEi/ARB.

Treatment:

Drug: tacrolimus

Drug: Corticosteroids

Biological: Simulect

Drug: tacrolimus

Drug: Cellcept