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

NCT ID: NCT00933231

Last Updated: 2024-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

281 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-08-17

Study Completion Date

2018-04-03

Brief Summary

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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.

Detailed Description

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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

Conditions

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Kidney Transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tacrolimus Standard Dose with ACEi/ARB

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

Group Type ACTIVE_COMPARATOR

tacrolimus

Intervention Type DRUG

Standard dose, Oral

Simulect

Intervention Type BIOLOGICAL

IV

Cellcept

Intervention Type DRUG

Oral

Corticosteroids

Intervention Type DRUG

IV and Oral

Ramipril

Intervention Type DRUG

Oral

Irbesartan

Intervention Type DRUG

Oral

Tacrolimus Standard Dose without ACEi/ARB

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

Group Type ACTIVE_COMPARATOR

tacrolimus

Intervention Type DRUG

Standard dose, Oral

Simulect

Intervention Type BIOLOGICAL

IV

Cellcept

Intervention Type DRUG

Oral

Corticosteroids

Intervention Type DRUG

IV and Oral

Tacrolimus Low Dose with ACEi/ARB

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

Group Type EXPERIMENTAL

tacrolimus

Intervention Type DRUG

Low dose, Oral

Simulect

Intervention Type BIOLOGICAL

IV

Cellcept

Intervention Type DRUG

Oral

Corticosteroids

Intervention Type DRUG

IV and Oral

Ramipril

Intervention Type DRUG

Oral

Irbesartan

Intervention Type DRUG

Oral

Tacrolimus Low Dose without ACEi/ARB

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

Group Type EXPERIMENTAL

tacrolimus

Intervention Type DRUG

Low dose, Oral

Simulect

Intervention Type BIOLOGICAL

IV

Cellcept

Intervention Type DRUG

Oral

Corticosteroids

Intervention Type DRUG

IV and Oral

Interventions

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tacrolimus

Standard dose, Oral

Intervention Type DRUG

tacrolimus

Low dose, Oral

Intervention Type DRUG

Simulect

IV

Intervention Type BIOLOGICAL

Cellcept

Oral

Intervention Type DRUG

Corticosteroids

IV and Oral

Intervention Type DRUG

Ramipril

Oral

Intervention Type DRUG

Irbesartan

Oral

Intervention Type DRUG

Other Intervention Names

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Advagraf FK506XL Prolonged Release Tacrolimus Tacrolimus XL Extended Release Tacrolimus FK506E MR4 Prolonged Release Tacrolimus FK506XL Extended Release Tacrolimus Tacrolimus XL FK506E MR4 Advagraf Basiliximab MMF Methylprednisolone prednisone Altace ACEi Avapro ARB

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Canada, Inc.

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Use Central Contact

Role: STUDY_DIRECTOR

Astellas Pharma Canada, Inc.

Locations

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Site CA133 Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

Site CA54 University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Site CA141 Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Site CA114 Capital District Health Authority- QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Site CA150 St. Joseph's Healthcare

Hamilton, Ontario, Canada

Site Status

Site CA27 London Health Sciences Centre

London, Ontario, Canada

Site Status

Site CA165 St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Site CA238 Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

Site CA172 Hôpital Notre-Dame du CHUM

Montreal, Quebec, Canada

Site Status

Site CA144 McGill University Health Centre

Montreal, Quebec, Canada

Site Status

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

Québec, Quebec, Canada

Site Status

Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont

Sherbrooke, Quebec, Canada

Site Status

Site CA142 St. Paul's Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type DERIVED
PMID: 39739990 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39082471 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30582281 (View on PubMed)

Related Links

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https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=315

Link to results on the Astellas Clinical Study Results website

Other Identifiers

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FKC-014

Identifier Type: -

Identifier Source: org_study_id

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