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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

This study is currently recruiting participants.
Verified March 2013 by Astellas Pharma Inc
Sponsor:
Collaborator:
Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00933231
First received: July 2, 2009
Last updated: March 25, 2013
Last verified: March 2013
History of Changes
  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 3

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:

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: March 2018
Estimated Primary Completion Date: September 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.:

  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
  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 (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
  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: March 25, 2013
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 hemisuccinate
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

ClinicalTrials.gov processed this record on May 21, 2013