Kidney-Pancreas TransplantationPhase 3NCT01797341
Prograf-Advagraf Cross Over Conversion Study
A Phase 3 study testing Tacrolimus in people with Kidney-Pancreas Transplantation, run by University Health Network, Toronto at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney-Pancreas Transplantation
- What is being tested?
- Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2013to Feb 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- episode of acute rejection within 6 months of screening
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients
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.
Read the 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.
- Conditions
- Kidney-Pancreas Transplantation
- Being tested
- Tacrolimus
- Keywords
- Renal Transplantation, Kidney transplantation, Pancreas Transplantation, Tacrolimus, Advagraf, Prograf, Drug Adherence
- Medical subject headings
- Medication Adherence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Prograf
TacrolimusDrug
Also called Advagraf
| Study group | Role | What they receive |
|---|---|---|
| Prograf arm | Experimental | 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. Receives: Drug: Tacrolimus |
| Advagraf Arm | Experimental | 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. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tacrolimus trough levels
Serum trough levels
Measured: prior to conversion and 12 weeks post-conversion
Change in Renal Function
Serum creatinine and urea levels
Measured: prior to conversion and 12 weeks post-conversion
Change in Tacrolimus dosage (week 12 compared to week 24)
Measured: week 12 and week 24
Secondary outcomes (5)
Change in Fasting glucose
serum fasting glucose levels
Measured: prior to conversion and 12 weeks post-conversion
Lipid profile
Cholesterol, etc...
Measured: prior to conversion and 12 weeks post-conversion
blood pressure
Cuff blood pressure readings
Measured: prior to conversion and 12 weeks post-conversion
Drug Adherence
patient self-reported drug adherence
Measured: assessed at weeks 12 and 24
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
Measured: at week 12 and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2013 (estimated)
- Study startJun 2013
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney-Pancreas TransplantationStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark S Cattral, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01797341
- Sponsor's protocol ID
- 12-0330-B
- Status last verified
- Jul 2014
- First submitted
- 11 Feb 2013
- Last updated
- 18 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients
- ClinicalTrials.gov ID
- NCT01797341
- Acronym / sponsor ID
- 12-0330-B
- Conditions
- Kidney-Pancreas Transplantation
- Keywords
- Renal Transplantation, Kidney transplantation, Pancreas Transplantation, Tacrolimus, Advagraf, Prograf, Drug Adherence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 22 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prograf arm | Experimental | Drug: Tacrolimuspatients 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. |
| Advagraf Arm | Experimental | Drug: Tacrolimuspatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (1 listed)
- episode of acute rejection within 6 months of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Prograf | Drug | Prograf arm |
| TacrolimusAlso: Advagraf | Drug | Advagraf Arm |
Primary outcome
Tacrolimus trough levels
Time frame: prior to conversion and 12 weeks post-conversion
Serum trough levels
Change in Renal Function
Time frame: prior to conversion and 12 weeks post-conversion
Serum creatinine and urea levels
Change in Tacrolimus dosage (week 12 compared to week 24)
Time frame: week 12 and week 24
5 secondary outcomes
Change in Fasting glucose
Time frame: prior to conversion and 12 weeks post-conversion
Lipid profile
Time frame: prior to conversion and 12 weeks post-conversion
blood pressure
Time frame: prior to conversion and 12 weeks post-conversion
Drug Adherence
Time frame: assessed at weeks 12 and 24
Number of Participants with Adverse Events as a Measure of Safety and Tolerability"
Time frame: at week 12 and week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark S Cattral, MD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus in people with Kidney-Pancreas Transplantation, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tacrolimus trough levels (time frame: prior to conversion and 12 weeks post-conversion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2014.