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

NCT00933231 | Completed Phase 3 DMC

• 1 other identifier: FKC-014
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Kidney Transplantation

Keywords

Tacrolimus; Kidney Transplantation; Advagraf; Immunosuppression; Angiotensin-Converting Enzyme Inhibitors

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with the Presence of Allograft Interstitial Fibrosis and Tubular Atrophy (IF/TA) as Assessed at a Central Pathology Lab

  up to 24 months

• Progression of IF/TA from Month 6 to Month 24

  up to 24 months

Secondary Outcomes (18)

• Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab

  up to 24 months

• Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology

  up to 24 months

• Percentage of Participants with Humoral Rejections

  up to 24 months

• Percentage of Participants with Acute Rejections

  up to 24 months

• Time to First Any Acute Rejection

  up to 24 months

Study Arms (4)

Tacrolimus Standard Dose with ACEi/ARB

ACTIVE COMPARATOR

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

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

Tacrolimus Standard Dose without ACEi/ARB

ACTIVE COMPARATOR

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

Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids

Tacrolimus Low Dose with ACEi/ARB

EXPERIMENTAL

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

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

Tacrolimus Low Dose without ACEi/ARB

EXPERIMENTAL

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

Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids

Interventions

tacrolimus DRUG

Standard dose, Oral

Also known as: Advagraf, FK506XL, Prolonged Release Tacrolimus, Tacrolimus XL, Extended Release Tacrolimus, FK506E, MR4

Tacrolimus Standard Dose with ACEi/ARB; Tacrolimus Standard Dose without ACEi/ARB

Simulect BIOLOGICAL

IV

Also known as: Basiliximab

Tacrolimus Low Dose with ACEi/ARB; Tacrolimus Low Dose without ACEi/ARB; Tacrolimus Standard Dose with ACEi/ARB; Tacrolimus Standard Dose without ACEi/ARB

Cellcept DRUG

Oral

Also known as: MMF

Tacrolimus Low Dose with ACEi/ARB; Tacrolimus Low Dose without ACEi/ARB; Tacrolimus Standard Dose with ACEi/ARB; Tacrolimus Standard Dose without ACEi/ARB

Corticosteroids DRUG

IV and Oral

Also known as: Methylprednisolone, prednisone

Tacrolimus Low Dose with ACEi/ARB; Tacrolimus Low Dose without ACEi/ARB; Tacrolimus Standard Dose with ACEi/ARB; Tacrolimus Standard Dose without ACEi/ARB

Ramipril DRUG

Oral

Also known as: Altace, ACEi

Tacrolimus Low Dose with ACEi/ARB; Tacrolimus Standard Dose with ACEi/ARB

Irbesartan DRUG

Oral

Also known as: Avapro, ARB

Tacrolimus Low Dose with ACEi/ARB; Tacrolimus Standard Dose with ACEi/ARB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Astellas Pharma Canada, Inc.: collaborator

Study Sites (13)

Site CA133 Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Site CA54 University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Site CA141 Health Sciences Centre

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Site CA114 Capital District Health Authority- QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Site CA150 St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

Site CA27 London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Site CA165 St. Michael's Hospital

Toronto, Ontario, M5C 2T2, Canada

Location

Site CA238 Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Site CA172 Hôpital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

Site CA144 McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Site CA64 Centre Hospitalier Universitaire de Québec- L'Hôtel-dieu de Québec

Québec, Quebec, G1R 2J6, Canada

Location

Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Site CA142 St. Paul's Hospital

Saskatoon, Saskatchewan, S7V 0Z9, Canada

Location

Related Publications (3)

• Campbell PM, Cantarovich M, Gangji A, Houde I, Jevnikar AM, Monroy-Cuadros FM, Nickerson PW, Paquet MR, Prasad GVR, Senecal L, Wolff JL, Schwartz JJ, Rush DN. A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus With or Without Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation. Clin Transplant. 2025 Jan;39(1):e70067. doi: 10.1111/ctr.70067.

  PMID: 39739990 DERIVED

• Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.

  PMID: 39082471 DERIVED

• Cockfield SM, Wilson S, Campbell PM, Cantarovich M, Gangji A, Houde I, Jevnikar AM, Keough-Ryan TM, Monroy-Cuadros FM, Nickerson PW, Paquet MR, Ramesh Prasad GV, Senecal L, Shoker A, Wolff JL, Howell J, Schwartz JJ, Rush DN. Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts. Am J Transplant. 2019 Jun;19(6):1730-1744. doi: 10.1111/ajt.15225. Epub 2019 Feb 1.

  PMID: 30582281 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Interventions

Tacrolimus; Basiliximab; Mycophenolic Acid; Adrenal Cortex Hormones; Methylprednisolone; Prednisone; Ramipril; Irbesartan

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Principal Investigator

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Use Central Contact

  Astellas Pharma Canada, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2009
• First Posted: July 7, 2009
• Study Start: August 17, 2009
• Primary Completion: May 11, 2015
• Study Completion: April 3, 2018
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (13)