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

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00933231
• Other study ID #: FKC-014
• Status: Completed
• Phase: Phase 3
• Start date: August 17, 2009
• Est. completion date: April 3, 2018

Study information

• Verified date: April 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 281
• Est. completion date: April 3, 2018
• Est. primary completion date: May 11, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• tacrolimus
Standard dose, Oral
• tacrolimus
Low dose, Oral

Biological:
• Simulect
IV

Drug:
• Cellcept
Oral
• Corticosteroids
IV and Oral
• Ramipril
Oral
• Irbesartan
Oral

Locations

Country	Name	City	State
Canada	Site CA133 Foothills Medical Centre	Calgary	Alberta
Canada	Site CA54 University of Alberta Hospital	Edmonton	Alberta
Canada	Site CA114 Capital District Health Authority- QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Site CA150 St. Joseph's Healthcare	Hamilton	Ontario
Canada	Site CA27 London Health Sciences Centre	London	Ontario
Canada	Site CA144 McGill University Health Centre	Montreal	Quebec
Canada	Site CA172 Hôpital Notre-Dame du CHUM	Montreal	Quebec
Canada	Site CA238 Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Site CA64 Centre Hospitalier Universitaire de Québec- L'Hôtel-dieu de Québec	Quebec
Canada	Site CA142 St. Paul's Hospital	Saskatoon	Saskatchewan
Canada	Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont	Sherbrooke	Quebec
Canada	Site CA165 St. Michael's Hospital	Toronto	Ontario
Canada	Site CA141 Health Sciences Centre	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	Astellas Pharma Canada, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Progression of IF/TA from Month 6 to Month 24		up to 24 months
Secondary	Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab		up to 24 months
Secondary	Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology		up to 24 months
Secondary	Percentage of Participants with Humoral Rejections		up to 24 months
Secondary	Percentage of Participants with Acute Rejections		up to 24 months
Secondary	Time to First Any Acute Rejection		up to 24 months
Secondary	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.	up to 24 months
Secondary	Change from Baseline in Chronic Allograft Damage Index		Baseline and 6, 24 months
Secondary	Percentage of Participants with Circulating Anti-Donor Antibody		up to 5 years
Secondary	Number of Participants with Cellular Immune Response (ELISPOT)		up to 6 months
Secondary	Urine Renal Biomarkers		up to 24 months
Secondary	Graft Survival		up to 5 years
Secondary	Patient Survival		up to 5 years
Secondary	Renal Function as Measured by Glomerular Filtration Rate (GFR)		up to 5 years
Secondary	Renal Function as Measured by Serum Creatinine		up to 5 years
Secondary	Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations		up to 5 years
Secondary	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.	up to 24 months
Secondary	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.	up to 24 months
Secondary	Percentage of Participants with Polyomavirus Infection		up to 12 months

External Links

•   Link to results on the Astellas Clinical Study Results website