Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk (ESTTEROD)
A One-Year, Prospective, Randomized, Controlled Study Evaluating The Efficacy Of Switching From The Twice Daily Tacrolimus Formulation To The Extended Release, Once Daily Formulation To Reduce The Framingham Cardiovascular Risk Scores.
Current standard prophylactic immunosuppression in renal transplantation includes tacrolimus, a calcineurin inhibitor, dosed twice daily. In Canada, oral tacrolimus has been available as a twice daily formulation marketed as Prograf® since 1997. It has recently become available in an extended release formulation called Advagraf®, which is dosed once daily. Advagraf® has been demonstrated to be therapeutically equivalent to Prograf® in the renal transplant maintenance population, and as a result it has been is approved as an alternative to the twice daily formulation in these patients. There is an evolving and expanding positive clinical experience with Advagraf® in kidney transplantation and it has shown to be preferred by many patients, due to the diminished dosing frequency. In clinical trials, Advagraf® has been shown to have other potential benefits over Prograf® such as less inter and intra-patient variability, improved cardiovascular profiles, and improved kidney function. Compared to Prograf®, Advagraf® also has a lower Cmin or 'trough' concentration as well as a lower Cmax or 'peak' concentration. The purpose of this study is to convert stabilized renal transplant patients currently receiving Prograf® to Advagraf®, to investigate these potential therapeutic benefits.
The Framingham Risk Score and the Reynold's Risk Score are currently recommended by the Canadian Cardiovascular Society (CCS) to predict 10-year cardiovascular risk in the general population. Surrogate markers are widely used in clinical trials to shorten follow-up durations. In this study, the investigators will use the Framingham Risk Score and Reynold's Risk Score to quantify changes in estimated cardiovascular risk. The investigators also intend to examine novel inflammatory markers to investigate cardiovascular risk.
The investigators hypothesize that the more consistent drug exposure and lower Cmax noted with Advagraf® will decrease Framingham Risk Score, Reynolds Risk score as well as markers of inflammation in kidney transplant recipients.
研究概览
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
-
-
Saskatchewan
-
Saskatoon、Saskatchewan、加拿大、S7M0Z9
- St Paul's Hospital
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Kidney transplant patients currently stable on the twice-daily formulation and who are followed as outpatients.
- Stability is defined as change in serum creatinine of less than 10% over the last two months
- Age 18-74 years old
- At least six months after transplantation
- Lack of 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 a clinical trial within the last 90 days
Exclusion Criteria:
- Patients with other types of solid organ transplants
- Patients with any form of substance abuse or psychiatric disorder.
- Patients with acute or chronic diarrhea
- Patients receiving anti-lymphocyte treatment for rejection within the last six months
- Patients on cyclosporine and or not receiving a mycophenolate derivative.
- 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, Hep C and HCV.
- Presence of any acute illness requiring admission to the hospital for the last 4 weeks
- Pregnancy
- Significant cardiovascular event such as MI, stroke or TIA within the last 12 weeks or uncontrolled hypertension.
- Immunosuppressant changes within the last month.
学习计划
研究是如何设计的？
设计细节
- 主要用途：支持治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Once Daily Tacrolimus
Treatment Arm - Subjects are switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
|
Subjects switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
其他名称：
|
|
有源比较器：Twice Daily Tacrolimus
Control Arm - Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
|
Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Change in the Framingham risk scores and change in the Reynolds Risk Score.
大体时间：Visit 1, Visit 3 (12 months)
|
Visit 1, Visit 3 (12 months)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Comparison in GFR between the two groups.
大体时间：Visit 1, Visit 3 (12 months)
|
Visit 1, Visit 3 (12 months)
|
|
|
Effect of therapy on CV biomarkers, insulin resistance and lipid profile.
大体时间：Visit 1, Visit 3 (12 months)
|
CV biomarkers will be assessed by luminex and insulin resistance and lipid profile will be assessed by the Metabolic Syndrome
|
Visit 1, Visit 3 (12 months)
|
|
To look at change in the glomerular filtration rate (GFR) over the duration of the study.
大体时间：Vist 1, Visit 3 (12 months)
|
Vist 1, Visit 3 (12 months)
|
合作者和调查者
调查人员
- 首席研究员：Ahmed Shoker, MD、University of Saskatchewan
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Once Daily Tacrolimus的临床试验
-
Birmingham Community Healthcare NHSNSA, LLC完全的
-
VA Office of Research and DevelopmentNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)主动，不招人
-
Galderma R&D完全的确定皮肤对 Cetaphil Daily Advance 超保湿乳液的敏感性
-
Andover Research Eye Institute完全的