Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk (ESTTEROD)
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.
|Immunosuppression Cardiovascular Diseases Kidney Transplantation||Drug: Once Daily Tacrolimus Drug: Twice Daily Tacrolimus||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||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.|
- Change in the Framingham risk scores and change in the Reynolds Risk Score. [ Time Frame: Visit 1, Visit 3 (12 months) ]
- Comparison in GFR between the two groups. [ Time Frame: Visit 1, Visit 3 (12 months) ]
- Effect of therapy on CV biomarkers, insulin resistance and lipid profile. [ Time Frame: 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
- To look at change in the glomerular filtration rate (GFR) over the duration of the study. [ Time Frame: Vist 1, Visit 3 (12 months) ]
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
Drug: Once Daily Tacrolimus
Subjects switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
Other Name: Advagraf®
Active Comparator: Twice Daily Tacrolimus
Control Arm - Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
Drug: Twice Daily Tacrolimus
Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
Other Name: Prograf®
Please refer to this study by its ClinicalTrials.gov identifier: NCT01702207
|St Paul's Hospital|
|Saskatoon, Saskatchewan, Canada, S7M0Z9|
|Principal Investigator:||Ahmed Shoker, MD||University of Saskatchewan|