Prograf-Advagraf Cross Over Conversion Study
Condition: Kidney-Pancreas Transplantation
Study type: Interventional
Phase: Phase 3

Summary: 
      The present study is aimed at evaluating the impact of a switch from Prograf to Advagraf on
      renal function, trough tacrolimus levels, drug-related adverse effects and adherence in
      stable recipients of kidney-pancreas transplants. MPA pharmacokinetics will also be
      evaluated. The results of this study have the potential to change current practice.
    

Detailed description: 
      Tacrolimus (Prograf ©) has become part of the standard of care for patients receiving solid
      organ transplants and is part of the immunosuppressive protocol used by kidney-pancreas
      transplant recipients at University Health Network (UHN). Tacrolimus is associated with
      several toxicities, and as a result, careful therapeutic drug monitoring of tacrolimus is a
      key component of post-transplant management. Trough serum concentrations of tacrolimus are
      measured routinely and are used to guide dosing. Tacrolimus trough levels are known to
      correlate with total drug exposure. The Prograf formulation of tacrolimus has a fairly short
      serum half-life and must be dosed twice daily to maintain therapeutic serum concentrations.
      This results in two high peak levels each day which have been shown to correlate with
      toxicity. Thus, avoidance of high peaks may be desirable to minimize tacrolimus toxicity.

      Advagraf is a new preparation of tacrolimus that is formulated to provide similar drug
      exposure to tacrolimus but with a once daily dosing regimen, which avoids the 2 daily high
      tacrolimus peaks observed with Prograf. In this way, it is hoped that Advagraf may provide
      similar therapeutic efficacy as Prograf but with fewer adverse effects. In addition, the
      simpler dosing regimen is expected to enhance patient adherence. Tacrolimus has also been
      shown, along with many other drugs, to have a variable impact on mycophenolate acid (MPA)
      pharmacokinetics. There are currently few data on whether Advagraf impacts MPA
      pharmacokinetics to the same or a lesser degree than Prograf.

      Eligible kidney-pancreas recipients will be recruited and after obtaining informed consent,
      randomized to continue their current total daily Prograf dosage or switch to the equivalent
      once daily dose of Advagraf. Patients will continue randomized therapy for 12 weeks and will
      then cross over to the opposite therapy for another 12 weeks. Patients will be followed and
      maintained on the same medication designated at week 24. Bloodwork results, adherence and AEs
      (adverse events) will be assessed.
    

Intervention name(s): Tacrolimus; Tacrolimus
Intervention type(s): Drug; Drug
Other intervention name(s): Prograf; Advagraf
Intervention MeSH terms: Tacrolimus
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Renal Transplantation; Kidney transplantation; Pancreas Transplantation; Tacrolimus; Advagraf; Prograf; Drug Adherence