Clinical trial NCT01797341: Prograf-Advagraf Cross Over Conversion Study
Official title: Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney-Pancreas Transplantation
Keywords: Renal Transplantation
Kidney transplantation
Pancreas Transplantation
Tacrolimus
Advagraf
Prograf
Drug Adherence
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2013-02-22
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* recipient of kidney and pancreas transplant
* aged 18 years or older
* 12 months or more since time of transplant
* stable allograft function (creatinine \< 180 µmol/l and eGFR \> 40 ml/min)
* targeted to a tacrolimus trough level of 5-10 ug/ml that has been stable during the prior 3 mo.

Exclusion Criteria:

* episode of acute rejection within 6 months of screening

Primary outcomes:
measure: Tacrolimus trough levels
timeFrame: prior to conversion and 12 weeks post-conversion
measure: Change in Renal Function
timeFrame: prior to conversion and 12 weeks post-conversion
measure: Change in Tacrolimus dosage (week 12 compared to week 24)
timeFrame: week 12 and week 24
Secondary outcomes:
measure: Change in Fasting glucose
timeFrame: prior to conversion and 12 weeks post-conversion
measure: Lipid profile
timeFrame: prior to conversion and 12 weeks post-conversion
measure: blood pressure
timeFrame: prior to conversion and 12 weeks post-conversion
measure: Drug Adherence
timeFrame: assessed at weeks 12 and 24
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability"
timeFrame: at week 12 and week 24
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Mark S Cattral, MD
role: PRINCIPAL_INVESTIGATOR
References: