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

Condition(s) targeted: Kidney Transplantation

Intervention: Advagraf (Drug); Advagraf (Drug); Simulect (Biological); Cellcept (Drug); Corticosteroids (Drug); Ramipril (Drug); Irbesartan (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Astellas Pharma Inc

Official(s) and/or principal investigator(s):
Use Central Contact, Study Director, Affiliation: Astellas Pharma Canada, Inc.

Overall contact:
Astellas Pharma Canada Inc., Medical Information, Phone: 888-338-1824

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.

Official title: 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

Study design: Treatment, Randomized, Open Label, Factorial Assignment, Safety/Efficacy Study

Primary outcome: The incidence of allograft interstitial fibrosis and tubular atrophy (IF/TA) as assessed at a central pathology lab

Secondary outcome:

The incidence of allograft IF/TA between 6 and 24 months as assessed at a central pathology lab

Renal function will be evaluated by estimation of GFR, serum creatinine, and urine protein:creatinine ratio

Blood pressure and the use of antihypertensive agents will be evaluated

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

1. Standard Advagraf dose with angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) antihypertensive therapy

2. Standard Advagraf dose without ACEi/ARB antihypertensive therapy

3. Low dose Advagraf with ACEi/ARB antihypertensive therapy

4. Lose dose Advagraf without ACEi/ARB antihypertensive therapy

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subject is the recipient of a first or second deceased or living donor mismatched (at

least one mismatch) renal transplant

- If female and of child-bearing potential, subject has a negative pregnancy test and

utilizes adequate contraceptive methods

Exclusion Criteria:

- Subjects with hepatitis B & C, HIV or cancer (excluding successfully excised squamous

or basal cell carcinoma)

- Recipient of a kidney from a donor over 65 years of age

- Recipient of non-related donor kidney with peak pre-transplant Panel Reactive

Antibodies >50

- Presence of donor specific antibody as detected by solid phase methodology

- 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

- Subjects who in the opinion of the Investigator, require ACEi/ARB therapy

post-transplant for any indication

- Subjects requiring induction with Thymoglobulin, Campath, antithymocyte globulin

(ATG), antilymphocyte globulin (ALG) or any other biological induction agent other than basiliximab

- Subject has plans to become pregnant within 2 years post-transplant

Astellas Pharma Canada Inc., Medical Information, Phone: 888-338-1824

Quebec G1R 2J6, Canada; Recruiting

Edmonton, Alberta T6G 2G3, Canada; Recruiting

Calgary, Alberta T2N 2T9, Canada; Recruiting

Winnipeg, Manitoba R3A 1R9, Canada; Recruiting

Toronto, Ontario M5C 2T2, Canada; Not yet recruiting

London, Ontario N6A 5A5, Canada; Not yet recruiting

Montreal, Quebec H3A 1A1, Canada; Not yet recruiting

Montreal, Quebec H2L 4M1, Canada; Not yet recruiting

Montreal, Quebec H1T 2M4, Canada; Recruiting

Sherbrooke, Quebec J1H 5N4, Canada; Not yet recruiting

Saskatoon, Saskatchewan S7V 0Z9, Canada; Not yet recruiting

Starting date: June 2009
Ending date: May 2016
Last updated: September 8, 2009