Prograf-Advagraf Cross Over Conversion Study

Kidney-Pancreas Transplantation Clinical Trial

Official title:

Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01797341
• Other study ID #: 12-0330-B
• Status: Completed
• Phase: Phase 3
• First received: February 11, 2013
• Last updated: September 17, 2014
• Start date: June 2013
• Est. completion date: February 2014

Study information

• Verified date: July 2014
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney-Pancreas Transplantation

Intervention

Drug:
• Tacrolimus

• Tacrolimus

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tacrolimus trough levels	Serum trough levels	prior to conversion and 12 weeks post-conversion	No
Primary	Change in Renal Function	Serum creatinine and urea levels	prior to conversion and 12 weeks post-conversion	Yes
Primary	Change in Tacrolimus dosage (week 12 compared to week 24)		week 12 and week 24	No
Secondary	Change in Fasting glucose	serum fasting glucose levels	prior to conversion and 12 weeks post-conversion	Yes
Secondary	Lipid profile	Cholesterol, etc...	prior to conversion and 12 weeks post-conversion	Yes
Secondary	blood pressure	Cuff blood pressure readings	prior to conversion and 12 weeks post-conversion	Yes
Secondary	Drug Adherence	patient self-reported drug adherence	assessed at weeks 12 and 24	Yes
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability"	at every visit, patients will be asked about and assessed for any adverse event development	at week 12 and week 24	Yes