Kidney Transplantation
Conditions
Keywords
Tacrolimus, Kidney Transplantation, Advagraf, Immunosuppression, Angiotensin-Converting Enzyme Inhibitors
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.
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
Interventions
Sponsors
Astellas Pharma Canada, Inc.
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Banff 2007 Individual Sub-scores | up to 24 months | 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. |
| Change from Baseline in Chronic Allograft Damage Index | Baseline and 6, 24 months | — |
| Percentage of Participants with Circulating Anti-Donor Antibody | up to 5 years | — |
| Number of Participants with Cellular Immune Response (ELISPOT) | up to 6 months | — |
| Urine Renal Biomarkers | up to 24 months | — |
| Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab | up to 24 months | — |
| Patient Survival | up to 5 years | — |
| Renal Function as Measured by Glomerular Filtration Rate (GFR) | up to 5 years | — |
| Renal Function as Measured by Serum Creatinine | up to 5 years | — |
| Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations | up to 5 years | — |
| 12-Item Short Form (SF-12) Health Survey: Physical Composite Score (PCS) and Mental Health Composite Score (MCS) | up to 24 months | 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. |
| Kidney Transplant Recipient Opinions of Immunosuppressive Medications Questionnaire | up to 24 months | 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. |
| Percentage of Participants with Polyomavirus Infection | up to 12 months | — |
| Graft Survival | up to 5 years | — |
| Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology | up to 24 months | — |
Countries
Canada
Outcome results
None listed