End Stage Renal DiseasePhase 4NCT00182559
The Vienna Prograf and Endothelial Progenitor Cell Study
A Phase 4 study testing Ciclosporin and Tacrolimus in people with End Stage Renal Disease, run by Medical University of Vienna at 1 site in Austria.
Trial summary
The aim of the study is to determine if the conversion from the immunosuppressive agent cyclosporine to tacrolimus contributes to an improvement of the cardiovascular risk factors, better kidney function and immune system. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Ciclosporin and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteAustria
- Study dates
- Apr 2004to May 2009
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is recipient of a deceased or living donor renal transplant (including retransplants) Patient is 18 years or age or older at the time of transplantation. Patient is at least 6 months post-transplant. Patient is on a cyclosporine-based immunosuppression regimen o combination with/without mycophenolate mofetil and/or steroids at study entry.
- Patient has a functioning renal allograft and estimated GFR≥39 mL/min/1.73m2 within four weeks prior to study entry.
- Patient has a stable graft function without biopsy proven acute rejection episode within 3 months prior to study entry.
- Patient has not experienced a cardiovascular event. Patient has fully been informed and has given written informed consent according to the International Conference on Harmonization, Good Clinical Practice.
- Females are not pregnant and agree to practice effective birth control while receiving immunosuppressant medication.
- Patient has indications for conversion at the investigators discretion or is suffering from cyclosporine associated side effects like hypertension, hyperlipidemia or cosmetic side effects.
Who cannot join
- Patient is recipient of a solid organ transplant other than the kidney. Patient has recurrence of primary renal disease, or de novo renal disease. Patient is pregnant or lactating. Patient had known or suspected malignancy (except for treated squamous and basal cell skin cancers) <5 years before study entry or a history of post-transplant lymphoproliferative disease (PTLD).
- Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of the study is to determine if the conversion from the immunosuppressive agent cyclosporine to tacrolimus contributes to an improvement of the cardiovascular risk factors, better kidney function and immune system.
Read the detailed description
In addition to hypertension, diabetes, hyperlipidemia and smoking, as well as other non-traditional risk factors such as elevated C-reactive protein, homocysteine, Lp(a), or reduced renal function, depletion of endothelial progenitor cells (EPC) in the peripheral circulation may represent another important explanation for the excess cardiovascular morbidity of kidney transplant recipients. In this context, the potential association of immunosuppressive therapy with EPCs in kidney transplant recipients deserves special consideration. The use of tacrolimus associated with a more favorable cardiovascular risk factors profile in terms of improved blood pressure and lipid levels in kidney transplant recipients compared to cyclosporine users. Therefore, one can speculate whether tacrolimus users might have greater EPC counts compared to patients treated with cyclosporine.
In a pilot study we cross-sectionally studied EPC counts in 90 stable, middle-aged kidney transplant recipients. From multivariate analyses, we found a independent inverse association between EPC counts and body mass index and systolic blood pressure. Statin use was associated with greater EPC counts, while patients receiving azathioprine had lower EPC counts. These findings raised the hypothesis whether EPCs are responsible, at least in part, for the well-established association between these factors and cardiovascular outcomes.
Cystatin C is superior to serum creatinine as a marker of kidney function since cystatin C is a more sensitive marker than serum creatine for small changes in glomerular filtration rate. Until now, there are no available data on the change of cystatin C as a measure of graft function after conversion of a cyclosporine based immunosuppressive regimen to tacrolimus.
There is accumulating evidence for an important pathogenetic role of donor-reactive antibodies in kidney allograft rejection. Recent studies suggest an anti-humoral activity of tacrolimus in the setting of chronic rejection. Recent findings suggest that in patients who are on cyclosporine, tacrolimus rescue therapy could efficiently inhibit antibody formation.
Objective 1: To evaluate the change in endothelial progenitor cell (EPC) count in kidney graft recipients converted from cyclosporine to tacrolimus.
Objective 2: To evaluate the change in cystatin C as a measure of renal function in kidney graft recipients converted from cyclosporine to tacrolimus.
Objective 3: To determine the effect of tacrolimus on humoral alloreactivity in kidney graft recipients Study design: A 2:1 randomized, parallel group, open-label, prospective trial comparing two different immunosuppressive regimens in approximately 148 patients. Group A: Convert to tacrolimus in combination with/without mycophenolate mofetil and/or steroids. Group B: Maintain cyclosporine in combination with/without mycophenolate mofetil and/or steroids. Patients will be followed up for 24 months after conversion.
In an amendment (August 2006) we registered pharmacogenetic analyses of the multi-drug resistance transporter 1 (MDR1) gene (gene symbol: ABCB1). The patients´ DNA is extracted from peripheral venous blood manually with industrial extraction kits. Two gene sections are amplified by polymerase chain reaction (PCR). Mutations are determined by restriction enzymes (restriction fragment length polymorphisms, RFLP).
- Conditions
- End Stage Renal Disease
- Being tested
- Ciclosporin, Tacrolimus
- Keywords
- kidney, transplantation, tacrolimus, cyclosporine, conversion
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiclosporinDrug
Also called Sandimmun Neoral
Maintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL.
TacrolimusDrug
Also called Prograf
Conversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids.
| Study group | Role | What they receive |
|---|---|---|
| Ciclosporin | Active comparator | Maintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL. Receives: Drug: Ciclosporin |
| Tacrolimus | Active comparator | Conversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in endothelial progenitor cells from baseline to month 24
The primary endpoint was the effect of conversion from ciclosporin to tacrolimus based immunosuppressive therapy on endothelial progenitor cell count at month 24.
Measured: Baseline and 24 months
Secondary outcomes (1)
Renal function at baseline and after 24 months
Changes in risk factors for cardiovascular outcomes like serum lipids, blood pressure, diabetes mellitus, serum C-reactive protein, body mass index. Safety was addressed according to the incidence of medical necessity to change immunosuppressive therapy, serious opportunistic infection, new-onset diabetes mellitus, cardiovascular events, malignancy, lymphoma and lymphoproliferative disease, gingival hyperplasia, hypertrichosis, alopecia, graft loss and death.
Measured: Baseline, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startApr 2004
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 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, M.D., Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00182559
- Sponsor's protocol ID
- 2004-004209-98
- Other IDs
- 393/2004, 2004
- Status last verified
- Feb 2014
- First submitted
- 10 Sep 2005
- Last updated
- 5 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Plischke M, Riegersperger M, Dunkler D, Heinze G, Kikic Z, Winkelmayer WC, Sunder-Plassmann G. Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial. PLoS One. 2015 Aug 13;10(8):e0135674. doi: 10.1371/journal.pone.0135674. eCollection 2015.
PubMed 26270340Riegersperger M, Plischke M, Steiner S, Seidinger D, Sengoelge G, Winkelmayer WC, Sunder-Plassmann G. Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients. Transplantation. 2013 Jun 15;95(11):1338-45. doi: 10.1097/TP.0b013e31828fabb3.
PubMed 23594858
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Vienna Prograf and Endothelial Progenitor Cell Study
- ClinicalTrials.gov ID
- NCT00182559
- Acronym / sponsor ID
- 2004-004209-98
- Conditions
- End Stage Renal Disease
- Keywords
- kidney, transplantation, tacrolimus, cyclosporine, conversion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Apr 2004
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 16 Sep 2005 (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 aim of the study is to determine if the conversion from the immunosuppressive agent cyclosporine to tacrolimus contributes to an improvement of the cardiovascular risk factors, better kidney function and immune system.
Detailed description
In addition to hypertension, diabetes, hyperlipidemia and smoking, as well as other non-traditional risk factors such as elevated C-reactive protein, homocysteine, Lp(a), or reduced renal function, depletion of endothelial progenitor cells (EPC) in the peripheral circulation may represent another important explanation for the excess cardiovascular morbidity of kidney transplant recipients. In this context, the potential association of immunosuppressive therapy with EPCs in kidney transplant recipients deserves special consideration. The use of tacrolimus associated with a more favorable cardiovascular risk factors profile in terms of improved blood pressure and lipid levels in kidney transplant recipients compared to cyclosporine users. Therefore, one can speculate whether tacrolimus users might have greater EPC counts compared to patients treated with cyclosporine.
In a pilot study we cross-sectionally studied EPC counts in 90 stable, middle-aged kidney transplant recipients. From multivariate analyses, we found a independent inverse association between EPC counts and body mass index and systolic blood pressure. Statin use was associated with greater EPC counts, while patients receiving azathioprine had lower EPC counts. These findings raised the hypothesis whether EPCs are responsible, at least in part, for the well-established association between these factors and cardiovascular outcomes.
Cystatin C is superior to serum creatinine as a marker of kidney function since cystatin C is a more sensitive marker than serum creatine for small changes in glomerular filtration rate. Until now, there are no available data on the change of cystatin C as a measure of graft function after conversion of a cyclosporine based immunosuppressive regimen to tacrolimus.
There is accumulating evidence for an important pathogenetic role of donor-reactive antibodies in kidney allograft rejection. Recent studies suggest an anti-humoral activity of tacrolimus in the setting of chronic rejection. Recent findings suggest that in patients who are on cyclosporine, tacrolimus rescue therapy could efficiently inhibit antibody formation.
Objective 1: To evaluate the change in endothelial progenitor cell (EPC) count in kidney graft recipients converted from cyclosporine to tacrolimus.
Objective 2: To evaluate the change in cystatin C as a measure of renal function in kidney graft recipients converted from cyclosporine to tacrolimus.
Objective 3: To determine the effect of tacrolimus on humoral alloreactivity in kidney graft recipients Study design: A 2:1 randomized, parallel group, open-label, prospective trial comparing two different immunosuppressive regimens in approximately 148 patients. Group A: Convert to tacrolimus in combination with/without mycophenolate mofetil and/or steroids. Group B: Maintain cyclosporine in combination with/without mycophenolate mofetil and/or steroids. Patients will be followed up for 24 months after conversion.
In an amendment (August 2006) we registered pharmacogenetic analyses of the multi-drug resistance transporter 1 (MDR1) gene (gene symbol: ABCB1). The patients´ DNA is extracted from peripheral venous blood manually with industrial extraction kits. Two gene sections are amplified by polymerase chain reaction (PCR). Mutations are determined by restriction enzymes (restriction fragment length polymorphisms, RFLP).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ciclosporin | Active comparator | Drug: CiclosporinMaintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL. |
| Tacrolimus | Active comparator | Drug: TacrolimusConversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient is recipient of a deceased or living donor renal transplant (including retransplants) Patient is 18 years or age or older at the time of transplantation. Patient is at least 6 months post-transplant. Patient is on a cyclosporine-based immunosuppression regimen o combination with/without mycophenolate mofetil and/or steroids at study entry.
- Patient has a functioning renal allograft and estimated GFR≥39 mL/min/1.73m2 within four weeks prior to study entry.
- Patient has a stable graft function without biopsy proven acute rejection episode within 3 months prior to study entry.
- Patient has not experienced a cardiovascular event. Patient has fully been informed and has given written informed consent according to the International Conference on Harmonization, Good Clinical Practice.
- Females are not pregnant and agree to practice effective birth control while receiving immunosuppressant medication.
Key exclusion criteria (2 listed)
- Patient is recipient of a solid organ transplant other than the kidney. Patient has recurrence of primary renal disease, or de novo renal disease. Patient is pregnant or lactating. Patient had known or suspected malignancy (except for treated squamous and basal cell skin cancers) <5 years before study entry or a history of post-transplant lymphoproliferative disease (PTLD).
- Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.
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 |
|---|---|---|
| CiclosporinAlso: Sandimmun NeoralMaintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL. | Drug | Ciclosporin |
| TacrolimusAlso: PrografConversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids. | Drug | Tacrolimus |
Primary outcome
Change in endothelial progenitor cells from baseline to month 24
Time frame: Baseline and 24 months
The primary endpoint was the effect of conversion from ciclosporin to tacrolimus based immunosuppressive therapy on endothelial progenitor cell count at month 24.
1 secondary outcome
Renal function at baseline and after 24 months
Time frame: Baseline, 24 months
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 5 Feb 2014.
- Derived from this study: PubMed 26270340Plischke M, Riegersperger M, Dunkler D, Heinze G, Kikic Z, Winkelmayer WC, Sunder-Plassmann G. Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial. PLoS One. 2015 Aug 13;10(8):e0135674. doi: 10.1371/journal.pone.0135674. eCollection 2015.
- Derived from this study: PubMed 23594858Riegersperger M, Plischke M, Steiner S, Seidinger D, Sengoelge G, Winkelmayer WC, Sunder-Plassmann G. Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients. Transplantation. 2013 Jun 15;95(11):1338-45. doi: 10.1097/TP.0b013e31828fabb3.
- Website of the Medical University ViennaLink provided by the sponsor.
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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.
Gere Sunder-Plassmann, M.D. principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ciclosporin and Tacrolimus in people with End Stage Renal Disease, run by Medical University of Vienna at 1 site in Austria.
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 6 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 5 Feb 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 Austria. 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 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?
Change in endothelial progenitor cells from baseline to month 24 (time frame: Baseline and 24 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 NCT00182559, which also lists 2 linked publications.
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 5 Feb 2014.