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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 ongoing, but not recruiting participants.
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: September 14, 2016
Last verified: September 2016
  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:


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 glomerular filtration rate (GFR), serum creatinine, and urine protein:creatinine ratio [ Time Frame: 1, 3, 6, 12 months and annually thereafter (Up to 5 years) ] [ 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 ]

Enrollment: 281
Study Start Date: June 2009
Estimated Study Completion Date: March 2018
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard dose Advagraf with ACEi/ARB
Standard dose Advagraf will be evaluated with ACEi/ARB
Drug: Advagraf
Standard dose, Oral
Other Names:
  • Extended Release Tacrolimus
  • Prolonged Release Tacrolimus
  • MR4
  • FK506XL
  • FK506E
  • Tacrolimus XL
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:
  • Altace
  • ACEi
Drug: Irbesartan
Oral
Other Names:
  • Avapro
  • ARB
Active Comparator: Standard dose Advagraf without ACEi/ARB
Standard dose Advagraf will be evaluated without ACEi/ARB
Drug: Advagraf
Standard dose, Oral
Other Names:
  • Extended Release Tacrolimus
  • Prolonged Release Tacrolimus
  • MR4
  • FK506XL
  • FK506E
  • Tacrolimus XL
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
Low dose Advagraf will be evaluated with ACEi/ARB
Drug: Advagraf
Low dose, Oral
Other Names:
  • Extended Release Tacrolimus
  • FK506E
  • Prolonged Release Tacrolimus
  • MR4
  • Tacrolimus XL
  • FK506XL
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:
  • Altace
  • ACEi
Drug: Irbesartan
Oral
Other Names:
  • Avapro
  • ARB
Experimental: Low-dose Advagraf without ACEi/ARB
Low dose Advagraf will be evaluated without ACEi/ARB
Drug: Advagraf
Low dose, Oral
Other Names:
  • Extended Release Tacrolimus
  • FK506E
  • Prolonged Release Tacrolimus
  • MR4
  • Tacrolimus XL
  • FK506XL
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 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
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Canada, Alberta
Site CA133 Foothills Medical Centre
Calgary, Alberta, Canada, T2N 2T9
Site CA54 University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, Manitoba
Site CA141 Health Sciences Centre
Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Nova Scotia
Site CA114 Capital District Health Authority- QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Site CA150 St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
Site CA27 London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Site CA165 St. Michael's Hospital
Toronto, Ontario, Canada, M5C 2T2
Canada, Quebec
Site CA238 Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Site CA172 Hôpital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Site CA144 McGill University Health Centre
Montreal, Quebec, Canada, H3A 1A1
Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Site CA142 St. Paul's Hospital
Saskatoon, Saskatchewan, Canada, S7V 0Z9
Canada
Site CA64 Centre Hospitalier Universitaire de Québec- L'Hôtel-dieu de Québec
Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Astellas Pharma Inc
Astellas Pharma Canada, Inc.
Investigators
Principal Investigator: Principal Investigator University of Alberta
Study Director: Use Central Contact Astellas Pharma Canada, Inc.
  More Information

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: September 14, 2016
Health Authority: Canada: Health Canada
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc:
Tacrolimus
Kidney Transplantation
Advagraf
Immunosuppression
Angiotensin-Converting Enzyme Inhibitors

Additional relevant MeSH terms:
Methylprednisolone
Tacrolimus
Mycophenolate mofetil
Basiliximab
Ramipril
Enzyme Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Irbesartan
Angiotensin Receptor Antagonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers

ClinicalTrials.gov processed this record on September 30, 2016