ImmunosuppressionPhase 4PEP-XNCT03751332
The Vienna Prograf and Endothelial Progenitor Cell Extension Study
A Phase 4 study testing Tacrolimus in people with Immunosuppression and Renal Failure, run by Medical University of Vienna.
Trial summary
Conversion of renal transplant recipients from either tacrolimus or cyclosporin A to tacrolimus modified release to investigate the effects of the MDR1/CYP450 genotype on the trough blood levels of tacrolimus with modified galenic (tacrolimus MR4; Advagraf®). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Immunosuppression, Renal Failure
- What is being tested?
- Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- No sites listed yet
- Study dates
- Mar 2008to Oct 2010
- Phase
- Phase 4
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any stable long-term kidney transplant recipient who participated in the Vienna Prograf and Endothelial-Progenitor Study (Vienna PEP Study; EudraCT identifier 2004-82 004209-98)
- Written informed consent to have the immunosuppression converted from either cyclosporin A or tacrolimus to tacrolimus modified-release
Who cannot join
- Graft failure
- Contraindication to receive immunosuppression
About this study
Conversion of renal transplant recipients from either tacrolimus or cyclosporin A to tacrolimus modified release to investigate the effects of the MDR1/CYP450 genotype on the trough blood levels of tacrolimus with modified galenic (tacrolimus MR4; Advagraf®).
Read the detailed description
The study concerns the conversion of immunosuppressive agents among participants in the clinical trial "The Vienna Prograf and Endothelial Progenitor Cell Study - The Vienna PEP Study" at the end of the study after 2 years in the extension study PEP-X.
The aim of the conversion is to investigate the effects of the multi-drug resistance (MDR1, gene symbol ABCB1) genotype on the trough blood levels of tacrolimus modified release (TAC MR4; Advagraf®). Analyzes of the effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d]) will be carried out, as well as studies on existing polymorphisms in the MDR1 gene. The written informed consent to conversion of either tacrolimus (TAC; Prograf®) or cyclosporin A (CSA; Sandimmun Neoral®) to TAC MR4 will be obtained.
Upon completion of 24 months of study participation of the PEP-study, and consent to convert the immunosuppressant therapy of either TAC or CSA to TAC MR4, it will be used as indicated by the manufacturer. In patients treated with CSA, the initial dose will be 0.1-0.12 mg TAC MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with TAC, the conversion to TAC MR4 will be performed in a 1:1 ratio.
The dosage data for the conversion of CSA to TAC MR4 are taken from the documents of the European Medicines Agency homepage (http://www.emea.europa.eu/index/ indexh1.htm, retrieved 26.09.2007), those on the safety and equivalence of the achieved areas under the curve (AUC) of both TAC formulations from Alloway et al. (Transplant Proc 2005; 37: 867-870).
The conversion will be performed by Univ. Prof. Dr. Gere Sunder-Plassmann, and Dr. Markus Riegersperger, respectively, both Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna. The desired trough level is set at 4.0-8.0ng/mL according to the usual clinical standards for long-term transplant patients at the investigators center. The trough level analyses are performed at the Medical University of Vienna, according to the following schedule: 1 week after conversion, 2 weeks after conversion, 4 weeks after conversion, 12 weeks and 12 months after conversion.
- Conditions
- Immunosuppression, Renal Failure
- Being tested
- Tacrolimus
- Keywords
- Calcineurin inhibitors, Tacrolimus modified release, Conversion, Trough levels, MDR-1
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Conversion from either cyclosporin or tacrolimus to tacrolimus modified release
| Study group | Role | What they receive |
|---|---|---|
| Conversion from either CSA or TAC | Other | Tacrolimus with modified galenic (tacrolimus MR4; Advagraf®) once daily. In patients treated with ciclosporin A, the initial dose will be 0.1 - 0.12 mg tacrolimus MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with Prograf, the conversion to Advagraf will be performed in a 1:1 ratio. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of the MDR1 genotype on the trough blood levels of tacrolimus with modified galenics (tacrolimus MR4; Advagraf®)
Effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d])
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study startMar 2008
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ImmunosuppressionStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gere Sunder-Plassmann, Medical University of Vienna
- Investigators
- Gere Sunder-Plassmann, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03751332
- Sponsor's protocol ID
- 1.05
- Other IDs
- 154/01/2008
- Acronym
- PEP-X
- Status last verified
- Nov 2018
- First submitted
- 9 Nov 2018
- Last updated
- 23 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Riegersperger M, Plischke M, Jallitsch-Halper A, Steinhauser C, Fodinger M, Winkelmayer WC, Dunkler D, Sunder-Plassmann G. A non-randomized trial of conversion from ciclosporin and tacrolimus to tacrolimus MR4 in stable long-term kidney transplant recipients: Graft function and influences of ABCB1 genotypes. PLoS One. 2019 Jul 2;14(7):e0218709. doi: 10.1371/journal.pone.0218709. eCollection 2019.
PubMed 31266056
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Vienna Prograf and Endothelial Progenitor Cell Extension Study
- ClinicalTrials.gov ID
- NCT03751332
- Acronym / sponsor ID
- PEP-X / 1.05
- Conditions
- Immunosuppression, Renal Failure
- Keywords
- Calcineurin inhibitors, Tacrolimus modified release, Conversion, Trough levels, MDR-1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Mar 2008 (actual)
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 23 Nov 2018 (actual)
- 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.
Conversion of renal transplant recipients from either tacrolimus or cyclosporin A to tacrolimus modified release to investigate the effects of the MDR1/CYP450 genotype on the trough blood levels of tacrolimus with modified galenic (tacrolimus MR4; Advagraf®).
Detailed description
The study concerns the conversion of immunosuppressive agents among participants in the clinical trial "The Vienna Prograf and Endothelial Progenitor Cell Study - The Vienna PEP Study" at the end of the study after 2 years in the extension study PEP-X.
The aim of the conversion is to investigate the effects of the multi-drug resistance (MDR1, gene symbol ABCB1) genotype on the trough blood levels of tacrolimus modified release (TAC MR4; Advagraf®). Analyzes of the effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d]) will be carried out, as well as studies on existing polymorphisms in the MDR1 gene. The written informed consent to conversion of either tacrolimus (TAC; Prograf®) or cyclosporin A (CSA; Sandimmun Neoral®) to TAC MR4 will be obtained.
Upon completion of 24 months of study participation of the PEP-study, and consent to convert the immunosuppressant therapy of either TAC or CSA to TAC MR4, it will be used as indicated by the manufacturer. In patients treated with CSA, the initial dose will be 0.1-0.12 mg TAC MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with TAC, the conversion to TAC MR4 will be performed in a 1:1 ratio.
The dosage data for the conversion of CSA to TAC MR4 are taken from the documents of the European Medicines Agency homepage (http://www.emea.europa.eu/index/ indexh1.htm, retrieved 26.09.2007), those on the safety and equivalence of the achieved areas under the curve (AUC) of both TAC formulations from Alloway et al. (Transplant Proc 2005; 37: 867-870).
The conversion will be performed by Univ. Prof. Dr. Gere Sunder-Plassmann, and Dr. Markus Riegersperger, respectively, both Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna. The desired trough level is set at 4.0-8.0ng/mL according to the usual clinical standards for long-term transplant patients at the investigators center. The trough level analyses are performed at the Medical University of Vienna, according to the following schedule: 1 week after conversion, 2 weeks after conversion, 4 weeks after conversion, 12 weeks and 12 months after conversion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Conversion from either CSA or TAC | Other | Drug: TacrolimusTacrolimus with modified galenic (tacrolimus MR4; Advagraf®) once daily. In patients treated with ciclosporin A, the initial dose will be 0.1 - 0.12 mg tacrolimus MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with Prograf, the conversion to Advagraf will be performed in a 1:1 ratio. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Any stable long-term kidney transplant recipient who participated in the Vienna Prograf and Endothelial-Progenitor Study (Vienna PEP Study; EudraCT identifier 2004-82 004209-98)
- Written informed consent to have the immunosuppression converted from either cyclosporin A or tacrolimus to tacrolimus modified-release
Key exclusion criteria (2 listed)
- Graft failure
- Contraindication to receive immunosuppression
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 |
|---|---|---|
| TacrolimusConversion from either cyclosporin or tacrolimus to tacrolimus modified release | Drug | Conversion from either CSA or TAC |
Primary outcome
Effects of the MDR1 genotype on the trough blood levels of tacrolimus with modified galenics (tacrolimus MR4; Advagraf®)
Time frame: 12 months
Effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d])
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 23 Nov 2018.
- Derived from this study: PubMed 31266056Riegersperger M, Plischke M, Jallitsch-Halper A, Steinhauser C, Fodinger M, Winkelmayer WC, Dunkler D, Sunder-Plassmann G. A non-randomized trial of conversion from ciclosporin and tacrolimus to tacrolimus MR4 in stable long-term kidney transplant recipients: Graft function and influences of ABCB1 genotypes. PLoS One. 2019 Jul 2;14(7):e0218709. doi: 10.1371/journal.pone.0218709. eCollection 2019.
- Individual participant dataSharing planned: Undecided
Related trials for Immunosuppression
Not yet recruitingPhase 1
Study of Disulfiram to Reduce Myeloid Immunosuppression and Steroid Dependence in Resectable High Grade Glioma
Brain (Nervous System) Cancers
Active, not recruitingPhase 3
RSV Vaccine in Transplant Recipients
Vaccine Response Impaired, Respiratory Syncytial Virus Infections
RecruitingObservational study
Metabolic and Functional Study of γδ T Cells in Critically Ill Patients
Sepsis, Critical Illness
Active, not recruitingPhase 2
Islet Cell Transplant for Type 1 Diabetes
Type 1 Diabetes Mellitus
Not yet recruitingObservational study
Microbiota Changes Related to Outcomes in Kidney Transplantation
End-stage Renal Disease (ESRD), Kidney Transplantation
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.
Gere Sunder-Plassmann, MD principal investigator
Medical University of Vienna
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus in people with Immunosuppression and Renal Failure, run by Medical University of Vienna.
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 2 inclusion and 2 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 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Effects of the MDR1 genotype on the trough blood levels of tacrolimus with modified galenics (tacrolimus MR4; Advagraf®) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03751332, which also lists 1 linked publication.
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 23 Nov 2018.