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Kidney TransplantationPhase 3NCT00933231

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

A Phase 3 study testing tacrolimus, Simulect and Cellcept in people with Kidney Transplantation, run by Astellas Pharma Inc at 13 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Kidney Transplantation
What is being tested?
tacrolimus, Simulect and Cellcept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
281 participants
Where
13 sitesCanada
Study dates
17 Aug 2009to 3 Apr 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Canada13 sites

  • Site CA133 Foothills Medical Centre

    Calgary, Alberta, T2N 2T9

  • Site CA54 University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • Site CA114 Capital District Health Authority- QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Site CA150 St. Joseph's Healthcare

    Hamilton, Ontario, L8N 4A6

  • Site CA27 London Health Sciences Centre

    London, Ontario, N6A 5A5

  • Site CA238 Hôpital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Site CA172 Hôpital Notre-Dame du CHUM

    Montreal, Quebec, H2L 4M1

  • Site CA144 McGill University Health Centre

    Montreal, Quebec, H4A 3J1

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

    Québec, Quebec, G1R 2J6

  • Site CA142 St. Paul's Hospital

    Saskatoon, Saskatchewan, S7V 0Z9

  • Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont

    Sherbrooke, Quebec, J1H 5N4

  • Site CA165 St. Michael's Hospital

    Toronto, Ontario, M5C 2T2

  • Site CA141 Health Sciences Centre

    Winnipeg, Manitoba, R3A 1R9

Other trials in Canada

About this study

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

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.

Read the 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
Being tested
tacrolimus, Simulect, Cellcept, Corticosteroids, Ramipril
Keywords
Tacrolimus, Kidney Transplantation, Advagraf, Immunosuppression, Angiotensin-Converting Enzyme Inhibitors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tacrolimusDrug

    Also called Advagraf, FK506XL, Prolonged Release Tacrolimus, Tacrolimus XL

    Standard dose, Oral

  • tacrolimusDrug

    Also called Prolonged Release Tacrolimus, FK506XL, Extended Release Tacrolimus, Tacrolimus XL

    Low dose, Oral

  • SimulectBiological

    Also called Basiliximab

    IV

  • CellceptDrug

    Also called MMF

    Oral

  • CorticosteroidsDrug

    Also called Methylprednisolone, prednisone

    IV and Oral

  • RamiprilDrug

    Also called Altace, ACEi

    Oral

  • IrbesartanDrug

    Also called Avapro, ARB

    Oral

Study groups in NCT00933231
Study groupRoleWhat they receive
Tacrolimus Standard Dose with ACEi/ARBActive comparatorParticipants receive a standard dose of tacrolimus with ACEi/ARB.
Receives: Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids; Drug: Ramipril; Drug: Irbesartan
Tacrolimus Standard Dose without ACEi/ARBActive comparatorParticipants receive a standard dose of tacrolimus without ACEi/ARB.
Receives: Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids
Tacrolimus Low Dose with ACEi/ARBExperimentalParticipants receive a low dose of tacrolimus with ACEi/ARB.
Receives: Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids; Drug: Ramipril; Drug: Irbesartan
Tacrolimus Low Dose without ACEi/ARBExperimentalParticipants receive a low dose of tacrolimus without ACEi/ARB.
Receives: Drug: tacrolimus; Biological: Simulect; Drug: Cellcept; Drug: Corticosteroids

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: up to 24 months

  2. Progression of IF/TA from Month 6 to Month 24

    Measured: up to 24 months

Secondary outcomes (18)

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

    Measured: up to 24 months

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

    Measured: up to 24 months

  3. Percentage of Participants with Humoral Rejections

    Measured: up to 24 months

  4. Percentage of Participants with Acute Rejections

    Measured: up to 24 months

  5. Time to First Any Acute Rejection

    Measured: up to 24 months

  6. Banff 2007 Individual Sub-scores

    Banff 2007 sub-scores (AH = Arteriolar hyalinethickening score; AT = Tubulitis score; AV = Intimal arteritis score; AI = Interstitial inflammation score; AG = Glomerulitis score; CG = Glomerulopathy score; CI = Interstitial fibrosis score; CT = Tubularatrophy score; CV = Vascular fibrous intimal thickening score; MM = Mesangial matrix increase score; TI = Total interstitial inflammation score; PTC = Peritubulary capillaritis score) is measured on an ordinal scale of 0 - 3.

    Measured: up to 24 months

  7. Change from Baseline in Chronic Allograft Damage Index

    Measured: Baseline and 6, 24 months

  8. Percentage of Participants with Circulating Anti-Donor Antibody

    Measured: up to 5 years

  9. Number of Participants with Cellular Immune Response (ELISPOT)

    Measured: up to 6 months

  10. Urine Renal Biomarkers

    Measured: up to 24 months

  11. Graft Survival

    Measured: up to 5 years

  12. Patient Survival

    Measured: up to 5 years

  13. Renal Function as Measured by Glomerular Filtration Rate (GFR)

    Measured: up to 5 years

  14. Renal Function as Measured by Serum Creatinine

    Measured: up to 5 years

  15. Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations

    Measured: up to 5 years

  16. 12-Item Short Form (SF-12) Health Survey: Physical Composite Score (PCS) and Mental Health Composite Score (MCS)

    The PCS and MCS are measured on a normalized 0-100 scale and computed using the corresponding subdomains from the SF-12 with 0 being the lowest level of health and 100 the highest.

    Measured: up to 24 months

  17. Kidney Transplant Recipient Opinions of Immunosuppressive Medications Questionnaire

    This questionnaire consists of 11 questions regarding immunosuppressive medications, where questions 1-3 ask about your experiences and opinions of transplant anti-rejection medications, questions 4 and 11 ask to rate each medication on the scale of 1-10, with 1 meaning disagree completely and 10 meaning agree completely, and questions 5-10 ask which medication satisfies the question.

    Measured: up to 24 months

  18. Percentage of Participants with Polyomavirus Infection

    Measured: up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2009 (estimated)
  2. Study start17 Aug 2009
  3. Primary completion11 May 2015
  4. Study completion3 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
281 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00933231
Sponsor's protocol ID
FKC-014
Status last verified
Oct 2024
First submitted
2 Jul 2009
Last updated
1 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • 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.

    PubMed 39739990

  • 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.

    PubMed 39082471

  • 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.

    PubMed 30582281

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tacrolimus, Simulect and Cellcept in people with Kidney Transplantation, run by Astellas Pharma Inc at 13 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with the Presence of Allograft Interstitial Fibrosis and Tubular Atrophy (IF/TA) as Assessed at a Central Pathology Lab (time frame: up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00933231, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2024.

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