Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk
Condition: Immunosuppression; Cardiovascular Diseases; Kidney Transplantation
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    


Intervention name(s): Once Daily Tacrolimus; Twice Daily Tacrolimus
Intervention type(s): Drug; Drug
Intervention description(s): Subjects switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.; Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
Other intervention name(s): Advagraf®; Prograf®
Intervention MeSH terms: Tacrolimus
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Prograf®; Advagraf®; tacrolimus; kidney transplant; renal transplant; cardiovascular risk; Framingham Risk; Reynolds Risk; immunosuppression