Comparisons Of Inflammatory Biomarkers And Cardiovascular Risk Scores Before And After Conversion To Full Dose Myfortic® Using Two Hour Neoral® Monitoring.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Change in Framingham score for renal transplant recipients.
研究概览
简要总结
The overall goal of this study is to improve cardiovascular outcomes in transplant recipients. The current standard immunosuppressive regimen in kidney transplant recipients depends on a higher exposure to the Calcineurin Inhibitor (CNI), and often a less than optimal dosage the of mycophenolic acid (MPA) derivative. The premise of this study is to investigate the effects of reversing this paradigm. More specifically, the effect of using maximum MPA dosages (in the form of enteric-coated mycophenolate sodium [EC-MPS] or Myfortic®) along with judicious CNI exposure (cyclosporine/Neoral®) will be investigated.
详细描述
Research Question:
Will treating kidney transplant recipients with maximum MPA dosages (in the form of EC-MPS or Myfortic®) along with judicious CNI exposure (cyclosporine/Neoral®) lead to improved cardiovascular outcomes, as measured by the Framingham Risk Score, 7-year major adverse cardiac events (MACE) score and cardiovascular risk inflammatory biomarker profile?
Primary Objectives:
- To improve the Framingham Risk Score and 7-year MACE score for renal transplant recipients, which estimate risk for cardiovascular disease.
- To improve the cardiovascular risk inflammatory biomarker profile.
Hypothesis:
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant patients followed as outpatients who are currently stabilized on immunosuppressive therapy with an MPA derivative, a CNI and prednisone where stability is defined as change in serum creatinine of less than 10% or over the last three months.
- •Age 18-74 years old.
- •At least six months after transplantation.
- •Lack of transplant rejection within the last 12 weeks.
- •Serum creatinine less than 300 umol/L at enrolment.
- •Negative urine pregnancy test for female patients of childbearing potential.
- •Consent to the study.
- •Not included in another interventional clinical trial within the last 90 days.
排除标准
- •Patients with other types of solid organ transplants.
- •Patients with any form of substance abuse or major psychiatric disorder.
- •Patients with acute or chronic diarrhea, known bowel disease or known gastroparesis.
- •Patients receiving anti-lymphocyte treatment for rejection within the last six months.
- •Patients not receiving a mycophenolic acid derivative.
- •Patients who do not tolerate the maximum Myfortic® total daily dose of 1440 mg OD.
- •Patients with significant liver disease defined as having an elevated bilirubin by at least two times the upper value of the normal range.
- •Patients who have any unstable medical condition that could interfere with the study.
- •Patients with chronic viral infection with HIV, Hepatitis B & C.
- •Presence of any acute illness requiring admission to the hospital for the last 4 weeks.
- •Significant cardiovascular event such as MI, stroke or TIA within the last 12 weeks or uncontrolled hypertension.
- •Immunosuppressant changes within the last month.
研究组 & 干预措施
Treatment Group
Maximization of mycophenolicacid (MPA) derivative (to a total daily dosage of 1440mg of Myfortic®) and reduction of cyclosporine dosage (as defined by C2 monitoring) in 50 stable renal transplant patients previously on immunosuppressive therapy with cyclosporine, an MPA derivative and prednisone.
干预措施: Myfortic® (Drug)
Treatment Group
Maximization of mycophenolicacid (MPA) derivative (to a total daily dosage of 1440mg of Myfortic®) and reduction of cyclosporine dosage (as defined by C2 monitoring) in 50 stable renal transplant patients previously on immunosuppressive therapy with cyclosporine, an MPA derivative and prednisone.
干预措施: Neoral® (Drug)
Control Group
25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.
干预措施: Myfortic® (Drug)
Control Group
25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.
干预措施: Cellcept® (Drug)
Control Group
25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.
干预措施: Prednisone (Drug)
结局指标
主要结局
Change in Framingham score for renal transplant recipients.
时间窗: 1 year
Cardiovascular risk factors using the Framingham 2009 risk score for renal transplant recipients and at end of the one year.
Surrogate markers for potential biological differences between the groups.
时间窗: 1 year
Cardiovascular (CV) Biomarkers compared between each group. CV Biomarkers of interest in this study include: 1. Chemokines (including ccl 1, 2, 15 and Clx 9 and 10) 2. Thrombopoitin 3. Cytokines IL 1, 2, 4, 6, 10, TGF, INF. These mediators are known to play a pivital role in atherosclerosis and progressive kidney failure.
Safety Measures
时间窗: 1 year
Safety will be measured by estimated Glomerular filtration rate (GFR).
Change in 7-year MACE score for renal transplant recipients.
时间窗: 1 year
Cardiovascular risk factors using the 7-year MACE calculator for renal transplant recipients and at end of the one year.
次要结局
未报告次要终点
研究者
AShoker
M.D.
University of Saskatchewan