Prograf-Advagraf Cross Over Conversion Study
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients|
- Tacrolimus trough levels [ Time Frame: prior to conversion and 12 weeks post-conversion ] [ Designated as safety issue: No ]Serum trough levels
- Change in Renal Function [ Time Frame: prior to conversion and 12 weeks post-conversion ] [ Designated as safety issue: Yes ]Serum creatinine and urea levels
- Change in Tacrolimus dosage (week 12 compared to week 24) [ Time Frame: week 12 and week 24 ] [ Designated as safety issue: No ]
- Change in Fasting glucose [ Time Frame: prior to conversion and 12 weeks post-conversion ] [ Designated as safety issue: Yes ]serum fasting glucose levels
- Lipid profile [ Time Frame: prior to conversion and 12 weeks post-conversion ] [ Designated as safety issue: Yes ]Cholesterol, etc...
- blood pressure [ Time Frame: prior to conversion and 12 weeks post-conversion ] [ Designated as safety issue: Yes ]Cuff blood pressure readings
- Drug Adherence [ Time Frame: assessed at weeks 12 and 24 ] [ Designated as safety issue: Yes ]patient self-reported drug adherence
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability" [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: Yes ]at every visit, patients will be asked about and assessed for any adverse event development
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Prograf arm
patients will self-administer tacrolimus in the form of Prograf (twice daily administration.
Dosage will be adjusted to maintain trough serum levels of 5-15 μg/ml. Maximum daily dose of 20 mg once per day.
Other Name: Prograf
Experimental: Advagraf Arm
patients will self-administer tacrolimus in the form of Advagraf (once daily dosing) Dosage will be adjusted to maintain trough serum levels of 5-15 μg/ml. Maximum daily dose of 20 mg once per day.
Other Name: Advagraf
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01797341
|Toronto General Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2N2|
|Contact: Andrea Norgate 416-340-4800 8866 email@example.com|
|Principal Investigator: Mark S Cattral, MD, F|
|Principal Investigator:||Mark S Cattral, MD||University Health Network, Toronto|