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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 281
- 试验地点
- 13
- 主要终点
- Percentage of Participants with the Presence of Allograft Interstitial Fibrosis and Tubular Atrophy (IF/TA) as Assessed at a Central Pathology Lab
研究概览
简要总结
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.
详细描述
The study will consist of the following 4 treatment groups.:
- Standard dose Advagraf with angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) antihypertensive therapy
- Standard dose Advagraf without ACEi/ARB antihypertensive therapy
- Low dose Advagraf with ACEi/ARB antihypertensive therapy
- Low dose Advagraf without ACEi/ARB antihypertensive therapy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: tacrolimus (Drug)
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: Simulect (Biological)
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: Cellcept (Drug)
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: Corticosteroids (Drug)
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: Ramipril (Drug)
Tacrolimus Standard Dose with ACEi/ARB
Participants receive a standard dose of tacrolimus with ACEi/ARB.
干预措施: Irbesartan (Drug)
Tacrolimus Standard Dose without ACEi/ARB
Participants receive a standard dose of tacrolimus without ACEi/ARB.
干预措施: tacrolimus (Drug)
Tacrolimus Standard Dose without ACEi/ARB
Participants receive a standard dose of tacrolimus without ACEi/ARB.
干预措施: Simulect (Biological)
Tacrolimus Standard Dose without ACEi/ARB
Participants receive a standard dose of tacrolimus without ACEi/ARB.
干预措施: Cellcept (Drug)
Tacrolimus Standard Dose without ACEi/ARB
Participants receive a standard dose of tacrolimus without ACEi/ARB.
干预措施: Corticosteroids (Drug)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: tacrolimus (Drug)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: Simulect (Biological)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: Cellcept (Drug)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: Corticosteroids (Drug)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: Ramipril (Drug)
Tacrolimus Low Dose with ACEi/ARB
Participants receive a low dose of tacrolimus with ACEi/ARB.
干预措施: Irbesartan (Drug)
Tacrolimus Low Dose without ACEi/ARB
Participants receive a low dose of tacrolimus without ACEi/ARB.
干预措施: tacrolimus (Drug)
Tacrolimus Low Dose without ACEi/ARB
Participants receive a low dose of tacrolimus without ACEi/ARB.
干预措施: Simulect (Biological)
Tacrolimus Low Dose without ACEi/ARB
Participants receive a low dose of tacrolimus without ACEi/ARB.
干预措施: Cellcept (Drug)
Tacrolimus Low Dose without ACEi/ARB
Participants receive a low dose of tacrolimus without ACEi/ARB.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Percentage of Participants with the Presence of Allograft Interstitial Fibrosis and Tubular Atrophy (IF/TA) as Assessed at a Central Pathology Lab
时间窗: up to 24 months
Progression of IF/TA from Month 6 to Month 24
时间窗: up to 24 months
次要结局
- Graft Survival(up to 5 years)
- Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations(up to 5 years)
- Time to First Any Acute Rejection(up to 24 months)
- Urine Renal Biomarkers(up to 24 months)
- 12-Item Short Form (SF-12) Health Survey: Physical Composite Score (PCS) and Mental Health Composite Score (MCS)(up to 24 months)
- Kidney Transplant Recipient Opinions of Immunosuppressive Medications Questionnaire(up to 24 months)
- Percentage of Participants with Polyomavirus Infection(up to 12 months)
- Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab(up to 24 months)
- Banff 2007 Individual Sub-scores(up to 24 months)
- Change from Baseline in Chronic Allograft Damage Index(Baseline and 6, 24 months)
- Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology(up to 24 months)
- Percentage of Participants with Acute Rejections(up to 24 months)
- Renal Function as Measured by Serum Creatinine(up to 5 years)
- Percentage of Participants with Humoral Rejections(up to 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)
- Patient Survival(up to 5 years)
- Renal Function as Measured by Glomerular Filtration Rate (GFR)(up to 5 years)