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 - Full Text View

Sponsor:	Astellas Pharma Inc
Collaborator:	Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00933231

Purpose

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.

Condition	Intervention	Phase
Kidney Transplantation	Drug: Advagraf Biological: Simulect Drug: Cellcept Drug: Corticosteroids Drug: Ramipril Drug: Irbesartan	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines Kidney Transplantation

Drug Information available for: Prednisolone Prednisolone acetate Prednisone Depo-medrol Medrol veriderm Ramipril Methylprednisolone Tacrolimus anhydrous Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Irbesartan Basiliximab Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone Corticosteroids

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:

The incidence of allograft interstitial fibrosis and tubular atrophy (IF/TA) as assessed at a central pathology lab [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The incidence of allograft IF/TA between 6 and 24 months as assessed at a central pathology lab [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
Renal function will be evaluated by estimation of GFR, serum creatinine, and urine protein:creatinine ratio [ Time Frame: 1, 3, 6, 12 months and annually thereafter ] [ Designated as safety issue: No ]
Blood pressure and the use of antihypertensive agents will be evaluated [ Time Frame: 1, 3, 6, 12 months and annually thereafter ] [ Designated as safety issue: No ]

Estimated Enrollment:	280
Study Start Date:	June 2009
Estimated Study Completion Date:	September 2017
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Standard dose Advagraf with ACEi/ARB	Drug: Advagraf Standard dose, Oral Other Names: Tacrolimus XL FK506XL FK506E MR4 Extended Release Tacrolimus Prolonged Release Tacrolimus Biological: Simulect IV Other Name: Basiliximab Drug: Cellcept Oral Other Name: MMF Drug: Corticosteroids IV and Oral Other Names: Methylprednisolone prednisone Drug: Ramipril Oral Other Names: ACEi Altace Drug: Irbesartan Oral Other Names: ARB Avapro
Active Comparator: Standard dose Advagraf without ACEi/ARB	Drug: Advagraf Standard dose, Oral Other Names: Tacrolimus XL FK506XL FK506E MR4 Extended Release Tacrolimus Prolonged Release Tacrolimus Biological: Simulect IV Other Name: Basiliximab Drug: Cellcept Oral Other Name: MMF Drug: Corticosteroids IV and Oral Other Names: Methylprednisolone prednisone
Experimental: Low-dose Advagraf with ACEi/ARB	Drug: Advagraf Low dose, Oral Other Names: Tacrolimus XL FK506XL FK506E MR4 Extended Release Tacrolimus Prolonged Release Tacrolimus Biological: Simulect IV Other Name: Basiliximab Drug: Cellcept Oral Other Name: MMF Drug: Corticosteroids IV and Oral Other Names: Methylprednisolone prednisone Drug: Ramipril Oral Other Names: ACEi Altace Drug: Irbesartan Oral Other Names: ARB Avapro
Experimental: Low-dose Advagraf without ACEi/ARB	Drug: Advagraf Low dose, Oral Other Names: Tacrolimus XL FK506XL FK506E MR4 Extended Release Tacrolimus Prolonged Release Tacrolimus Biological: Simulect IV Other Name: Basiliximab Drug: Cellcept Oral Other Name: MMF Drug: Corticosteroids IV and Oral Other Names: Methylprednisolone prednisone

Detailed Description:

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

Standard Advagraf dose with angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) antihypertensive therapy
Standard Advagraf dose without ACEi/ARB antihypertensive therapy
Low dose Advagraf with ACEi/ARB antihypertensive therapy
Lose dose Advagraf without ACEi/ARB antihypertensive therapy

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject is the recipient of a first or second deceased or living donor renal transplant
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933231

Contacts

Contact: Astellas Pharma Canada Inc., Medical Information

888-338-1824

Locations

Canada, Alberta
Foothills Medical Centre	Recruiting
Calgary, Alberta, Canada, T2N 2T9
University of Alberta Hospital	Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Canada, Manitoba
Health Sciences Centre	Recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Nova Scotia
Capital District Health Authority	Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
St. Joseph's Healthcare	Recruiting
Hamilton, Ontario, Canada, L8N 4A6
London Health Sciences Centre	Recruiting
London, Ontario, Canada, N6A 5A5
St. Michael's Hospital	Recruiting
Toronto, Ontario, Canada, M5C 2T2
Canada, Quebec
McGill University Health Centre	Recruiting
Montreal, Quebec, Canada, H3A 1A1
Hôpital Notre-Dame du CHUM	Recruiting
Montreal, Quebec, Canada, H2L 4M1
Hôpital Maisonneuve-Rosemont	Recruiting
Montreal, Quebec, Canada, H1T 2M4
Centre Hospitalier Universitaire de Sherbrooke (CHUS)-Hopital Fleurimont	Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
St. Paul's Hospital	Recruiting
Saskatoon, Saskatchewan, Canada, S7V 0Z9
Canada
Centre Hospitalier Universitaire de Québec	Recruiting
Quebec, Canada, G1R 2J6

Sponsors and Collaborators

Astellas Pharma Inc

Astellas Pharma Canada, Inc.

Investigators

Study Director:	Use Central Contact	Astellas Pharma Canada, Inc.
Principal Investigator:	Principal Investigator	University of Alberta

More Information

No publications provided

Responsible Party:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00933231 History of Changes
Other Study ID Numbers:	FKC-014
Study First Received:	July 2, 2009
Last Updated:	December 9, 2011
Health Authority:	Canada: Health Canada

Keywords provided by Astellas Pharma Inc:

Kidney Transplantation
Tacrolimus
Angiotensin-Converting Enzyme Inhibitors
Advagraf
Immunosuppression

Additional relevant MeSH terms:

Angiotensin-Converting Enzyme Inhibitors
Ramipril
Irbesartan
Antihypertensive Agents
Enzyme Inhibitors
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone phosphate
Mycophenolate mofetil
Tacrolimus
Basiliximab
Angiotensin Receptor Antagonists

Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids

ClinicalTrials.gov processed this record on February 09, 2012