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

October 30, 2024 updated by: Astellas Pharma Inc

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
281

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1R 2J6
        • Site CA64 Centre Hospitalier Universitaire de Québec- L'Hôtel-dieu de Québec
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Site CA133 Foothills Medical Centre
      • Edmonton, Alberta, Canada, T6G 2B7
        • Site CA54 University of Alberta Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Site CA141 Health Sciences Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Site CA114 Capital District Health Authority- QEII Health Sciences Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • Site CA150 St. Joseph's Healthcare
      • London, Ontario, Canada, N6A 5A5
        • Site CA27 London Health Sciences Centre
      • Toronto, Ontario, Canada, M5C 2T2
        • Site CA165 St. Michael's Hospital
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Site CA238 Hôpital Maisonneuve-Rosemont
      • Montreal, Quebec, Canada, H2L 4M1
        • Site CA172 Hôpital Notre-Dame du CHUM
      • Montreal, Quebec, Canada, H4A 3J1
        • Site CA144 McGill University Health Centre
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7V 0Z9
        • Site CA142 St. Paul's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
Drug: tacrolimus
Standard dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Drug: tacrolimus
Low dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Biological: Simulect
IV
Other Names:
  • Basiliximab
Drug: Cellcept
Oral
Other Names:
  • MMF
Drug: Corticosteroids
IV and Oral
Other Names:
  • Methylprednisolone
  • prednisone
Drug: Ramipril
Oral
Other Names:
  • Altace
  • ACEi
Drug: Irbesartan
Oral
Other Names:
  • Avapro
  • ARB
Active Comparator: Tacrolimus Standard Dose without ACEi/ARB
Participants receive a standard dose of tacrolimus without ACEi/ARB.
Drug: tacrolimus
Standard dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Drug: tacrolimus
Low dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Biological: Simulect
IV
Other Names:
  • Basiliximab
Drug: Cellcept
Oral
Other Names:
  • MMF
Drug: Corticosteroids
IV and Oral
Other Names:
  • Methylprednisolone
  • prednisone
Experimental: Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
Drug: tacrolimus
Standard dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Drug: tacrolimus
Low dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Biological: Simulect
IV
Other Names:
  • Basiliximab
Drug: Cellcept
Oral
Other Names:
  • MMF
Drug: Corticosteroids
IV and Oral
Other Names:
  • Methylprednisolone
  • prednisone
Drug: Ramipril
Oral
Other Names:
  • Altace
  • ACEi
Drug: Irbesartan
Oral
Other Names:
  • Avapro
  • ARB
Experimental: Tacrolimus Low Dose without ACEi/ARB
Participants receive a low dose of tacrolimus without ACEi/ARB.
Drug: tacrolimus
Standard dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Drug: tacrolimus
Low dose, Oral
Other Names:
  • Advagraf
  • FK506E
  • MR4
  • Extended Release Tacrolimus
  • FK506XL
  • Prolonged Release Tacrolimus
  • Tacrolimus XL
Biological: Simulect
IV
Other Names:
  • Basiliximab
Drug: Cellcept
Oral
Other Names:
  • MMF
Drug: Corticosteroids
IV and Oral
Other Names:
  • Methylprednisolone
  • prednisone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome 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
Time Frame: up to 24 months
up to 24 months
Progression of IF/TA from Month 6 to Month 24
Time Frame: up to 24 months
up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab
Time Frame: up to 24 months
up to 24 months
Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology
Time Frame: up to 24 months
up to 24 months
Percentage of Participants with Humoral Rejections
Time Frame: up to 24 months
up to 24 months
Percentage of Participants with Acute Rejections
Time Frame: up to 24 months
up to 24 months
Time to First Any Acute Rejection
Time Frame: up to 24 months
up to 24 months
Banff 2007 Individual Sub-scores
Time Frame: 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.
up to 24 months
Change from Baseline in Chronic Allograft Damage Index
Time Frame: Baseline and 6, 24 months
Baseline and 6, 24 months
Percentage of Participants with Circulating Anti-Donor Antibody
Time Frame: up to 5 years
up to 5 years
Number of Participants with Cellular Immune Response (ELISPOT)
Time Frame: up to 6 months
up to 6 months
Urine Renal Biomarkers
Time Frame: up to 24 months
up to 24 months
Graft Survival
Time Frame: up to 5 years
up to 5 years
Patient Survival
Time Frame: up to 5 years
up to 5 years
Renal Function as Measured by Glomerular Filtration Rate (GFR)
Time Frame: up to 5 years
up to 5 years
Renal Function as Measured by Serum Creatinine
Time Frame: up to 5 years
up to 5 years
Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations
Time Frame: up to 5 years
up to 5 years
12-Item Short Form (SF-12) Health Survey: Physical Composite Score (PCS) and Mental Health Composite Score (MCS)
Time Frame: 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.
up to 24 months
Kidney Transplant Recipient Opinions of Immunosuppressive Medications Questionnaire
Time Frame: 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.
up to 24 months
Percentage of Participants with Polyomavirus Infection
Time Frame: up to 12 months
up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Astellas Pharma Inc

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Astellas Pharma Canada, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Principal Investigator, University of Alberta
  • Study Director: Use Central Contact, Astellas Pharma Canada, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 17, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 11, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 2, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2009

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 7, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FKC-014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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/.

IPD Sharing Time Frame

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

IPD Sharing Access Criteria

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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