Prograf-Advagraf Cross Over Conversion Study

This study is currently recruiting participants.
Verified July 2013 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01797341
First received: February 11, 2013
Last updated: July 24, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Kidney-Pancreas Transplantation
Drug: Tacrolimus
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 40
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)
Arms Assigned Interventions
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.

Drug: Tacrolimus
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.
Drug: Tacrolimus
Other Name: Advagraf

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01797341

Locations
Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Andrea Norgate    416-340-4800 8866    andrea.norgate@uhn.ca   
Principal Investigator: Mark S Cattral, MD, F         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Mark S Cattral, MD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01797341     History of Changes
Other Study ID Numbers: 12-0330-B
Study First Received: February 11, 2013
Last Updated: July 24, 2013
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Renal Transplantation
Kidney transplantation
Pancreas Transplantation
Tacrolimus
Advagraf
Prograf
Drug Adherence

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014