Renal TransplantationPhase 4CISTCERTNCT00903188
Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation
A Phase 4 study testing cyclosporine and Everolimus in people with Renal Transplantation, run by University Hospital, Antwerp at 5 sites in Belgium.
Trial summary
This study intends to determine whether steroid withdrawal or calcineurin inhibitor withdrawal is superior for graft function and graft survival. Secondary endpoints for this study are: incidence of tumors and cardiovascular events. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- cyclosporine and Everolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 5 sitesBelgium
- Study dates
- Oct 2008to Apr 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female recipients of a de novo kidney transplant, aged above 18 years
- Women of childbearing potential must have a negative serum or urine pregnancy test with sensitivity equal to at least 50 mIU/ml
- Patients must be capable of understanding the purpose and risks of the study, and must sign an informed consent form
Who cannot join
- Multiple organ transplantation (e.g., Kidney-pancreas, kidney-heart, kidney- liver,...)
- Transplantation of a patient who got another organ transplant previously
- Recipients of a HLA-identical living-related renal transplant
- Patients with PRA > 30%, patients who have lost a first graft from rejection within two years after transplantation, and African European patients.
- Patients with primary renal disease at risk for recurrence: FSGS, MPGN, HUS
- Pregnant or lactating women
Show all 13Show fewer
- WBC < 2.5 x 109/l (IU), platelet count < 100 x 109/l (IU), or Hb < 6 g/dl at the time of entry into the study
- Active peptic ulcer
- Severe diarrhea or other gastrointestinal disorder, which might interfere with their ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy
- Known HIV-1 or HTLV-1 positive tests
- The use of investigational drugs or other immunosuppressive drugs, as those specified in this protocol
- Patients receiving bile acid sequestrants
- Psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Belgium5 sites, 5 recruiting
- Recruiting
Erasme University Hospital
Brussels, 1070
Daniel Abramowicz, MD/PhD, +32/2/555 35 32, dabram@ulb.ac.be
Daniel Abramowicz, MD/PhD
- Recruiting
University Hospital Brussels
Brussels, 1090
Jacques Sennesael, MD/PhD, +32/2/477 60 55, Jacques.Sennesael@uzbrussel.be
Jacques Sennesael, MD
- Recruiting
University Hospital Antwerp
Edegem, 2650
Jean-Louis Bosmans, MD/PhD, +32/3/821 37 92, jeanlouis.bosmans@ua.ac.be
Angelika Jurgens, Study Coord., +32/3/821 34 21, Angelika.Jurgens@uza.be
- Recruiting
University Hospital, Ghent
Ghent, 9000
Patrick Peeters, MD/PhD, +32/9/332 45 13, patrick.peeters@ugent.be
Patrick Peeters, MD
- Recruiting
University Hospital of Liege
Liège, 4000
Catherine Bonvoisin, MD/PhD, +32/4/366 82 58, catherine.bonvoisin@chu.ulg.ac.be
Catherine Bonvoisin, MD
About this study
Official title: Impact of Cyclosporine or Steroid Withdrawal at 3 Months Post Transplantation on Graft Function, Patient Survival and Cardiovascular Surrogate Markers the First 5 Years After Renal Transplantation.
This study intends to determine whether steroid withdrawal or calcineurin inhibitor withdrawal is superior for graft function and graft survival. Secondary endpoints for this study are: incidence of tumors and cardiovascular events.
The primary objective: To assess if superior graft function (glomerular filtration rate (GFR) difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.
Read the detailed description
Methodology:
- A 5-year, multicentre, prospective, randomized, open-label, controlled study
- Group 1: Simulect + cyclosporine + Myfortic + steroid stop at 3 months
- Group 2: Simulect + cyclosporine (decrease dose in one week at month 3 and replace by everolimus) + Myfortic + steroid maintenance.
- In both groups MPA AUC monitoring will be done at 5-7 days and at 3 months, to ensure sufficient MPA protection.
Sample size calculations:
A total of 152 patients will be randomized (76 patients per group)
Population:
De novo kidney transplant recipients.
Study duration:
1.5 years inclusion+ follow-up during the first 5 years
- Conditions
- Renal Transplantation
- Being tested
- cyclosporine, Everolimus
- Keywords
- Renal Transplantation, graft function, cardiovascular events, malignancy, cyclosporin, steroids, mycophenolate, everolimus, renal biopsies, pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporineDrug
Also called Neoral, Myfortic, Solumedrol, Medrol
Cyclosporine (Group 1):
basiliximab dose: 1x20 mg IV on Day 0 and 1x20 mg IV on Day 4
Cyclosporine: 8 mg/kg PO given before surgery, followed by 2x4 mg/kg/d. C-0h levels: month 1: 150-250 ng/ml; month 2: 100-200 ng/ml; month 3: withdrawal steroids: 100-150 ng/ml.
C-2h levels: month 1: 900-1100 ng/ml; month 2: 800-1000 ng/ml; month 3: withdrawal steroids: maintain level of 750 ng/ml
Enteric-coated mycophenolate(MPA):720mg PO pre-operatively followed by 1.44 g/day.
Steroids: pre-operatively: 250mg methylprednisolone IV; day 1:125mg IV.
Methylprednisolone:day 2-30:PO 12mg/d; day 31-60:tapered to 8mg/d ,day 61-90 :4mg/d; Month 3:stop
EverolimusDrug
Also called Certican, Neoral, Myfortic, Solumedrol
Everolimus (Group 2):
Basiliximab dose: idem as in group 1
Cyclosporine: first three months idem group 1; month 3: decreased dose by 50%, simultaneously initiate everolimus at a starting dose of 0.75 mg bid.
Once the everolimus blood levels range 6 - 12 ng/ml, cyclosporine will be stopped.
Enteric-coated mycophenolate (MPA) dosing idem as group 1.
Everolimus starting dose: 0.75 mg bid, trough levels: 6-12 ng/ml.
Steroid dosing: idem group 1, but maintained at 4 mg methylprednisolone after day 60.
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporine | Active comparator | Simulect + cyclosporine + Myfortic + steroid stop at 3 months Receives: Drug: cyclosporine |
| Everolimus | Active comparator | Simulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess if superior graft function (GFR difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.
Measured: 1 year
Secondary outcomes (1)
To compare the evolution of graft function (estimated GFR by means of modified MDRD formula)during the first 5 years post transplantation.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2009 (estimated)
- Study startOct 2008
- Primary completionApr 2010 (estimated)
- Study completionApr 2015 (estimated)
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 Renal TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Erasme University Hospital, University Hospital, Ghent, University of Liege, Universitair Ziekenhuis Brussel
- Investigators
- Jean-Louis Bosmans, MD/PhD, Principal investigator, University Hospital Antwerp - Department Nephrology-Hypertension
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903188
- Sponsor's protocol ID
- 2007-005844-26
- Acronym
- CISTCERT
- Status last verified
- May 2009
- First submitted
- 15 May 2009
- Last updated
- 18 May 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Pipeleers L, Abramowicz D, Broeders N, Lemoine A, Peeters P, Van Laecke S, Weekers LE, Sennesael J, Wissing KM, Geers C, Bosmans JL. 5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients. Transpl Int. 2021 Feb;34(2):313-326. doi: 10.1111/tri.13798. Epub 2020 Dec 31.
PubMed 33277746
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Cyclosporine or Steroid Withdrawal at 3 Months Post Transplantation on Graft Function, Patient Survival and Cardiovascular Surrogate Markers the First 5 Years After Renal Transplantation.
- ClinicalTrials.gov ID
- NCT00903188
- Acronym / sponsor ID
- CISTCERT / 2007-005844-26
- Conditions
- Renal Transplantation
- Keywords
- Renal Transplantation, graft function, cardiovascular events, malignancy, cyclosporin, steroids, mycophenolate, everolimus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Erasme University Hospital, University Hospital, Ghent, University of Liege, Universitair Ziekenhuis Brussel
- Study start
- Oct 2008
- Primary completion
- Apr 2010 (estimated)
- Study completion
- Apr 2015 (estimated)
- First posted
- 18 May 2009 (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.
This study intends to determine whether steroid withdrawal or calcineurin inhibitor withdrawal is superior for graft function and graft survival. Secondary endpoints for this study are: incidence of tumors and cardiovascular events.
The primary objective: To assess if superior graft function (glomerular filtration rate (GFR) difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.
Detailed description
Methodology:
- A 5-year, multicentre, prospective, randomized, open-label, controlled study
- Group 1: Simulect + cyclosporine + Myfortic + steroid stop at 3 months
- Group 2: Simulect + cyclosporine (decrease dose in one week at month 3 and replace by everolimus) + Myfortic + steroid maintenance.
- In both groups MPA AUC monitoring will be done at 5-7 days and at 3 months, to ensure sufficient MPA protection.
Sample size calculations:
A total of 152 patients will be randomized (76 patients per group)
Population:
De novo kidney transplant recipients.
Study duration:
1.5 years inclusion+ follow-up during the first 5 years
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporine | Active comparator | Drug: cyclosporineSimulect + cyclosporine + Myfortic + steroid stop at 3 months |
| Everolimus | Active comparator | Drug: EverolimusSimulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female recipients of a de novo kidney transplant, aged above 18 years
- Women of childbearing potential must have a negative serum or urine pregnancy test with sensitivity equal to at least 50 mIU/ml
- Patients must be capable of understanding the purpose and risks of the study, and must sign an informed consent form
Key exclusion criteria (13 listed)
- Multiple organ transplantation (e.g., Kidney-pancreas, kidney-heart, kidney- liver,...)
- Transplantation of a patient who got another organ transplant previously
- Recipients of a HLA-identical living-related renal transplant
- Patients with PRA > 30%, patients who have lost a first graft from rejection within two years after transplantation, and African European patients.
- Patients with primary renal disease at risk for recurrence: FSGS, MPGN, HUS
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 |
|---|---|---|
| cyclosporineAlso: Neoral, Myfortic, Solumedrol, MedrolCyclosporine (Group 1): basiliximab dose: 1x20 mg IV on Day 0 and 1x20 mg IV on Day 4 Cyclosporine: 8 mg/kg PO given before surgery, followed by 2x4 mg/kg/d. C-0h levels: month 1: 150-250 ng/ml; month 2: 100-200 ng/ml; month 3: withdrawal steroids: 100-150 ng/ml. C-2h levels: month 1: 900-1100 ng/ml; month 2: 800-1000 ng/ml; month 3: withdrawal steroids: maintain level of 750 ng/ml Enteric-coated mycophenolate(MPA):720mg PO pre-operatively followed by 1.44 g/day. Steroids: pre-operatively: 250mg methylprednisolone IV; day 1:125mg IV. Methylprednisolone:day 2-30:PO 12mg/d; day 31-60:tapered to 8mg/d ,day 61-90 :4mg/d; Month 3:stop | Drug | Cyclosporine |
| EverolimusAlso: Certican, Neoral, Myfortic, SolumedrolEverolimus (Group 2): Basiliximab dose: idem as in group 1 Cyclosporine: first three months idem group 1; month 3: decreased dose by 50%, simultaneously initiate everolimus at a starting dose of 0.75 mg bid. Once the everolimus blood levels range 6 - 12 ng/ml, cyclosporine will be stopped. Enteric-coated mycophenolate (MPA) dosing idem as group 1. Everolimus starting dose: 0.75 mg bid, trough levels: 6-12 ng/ml. Steroid dosing: idem group 1, but maintained at 4 mg methylprednisolone after day 60. | Drug | Everolimus |
Primary outcome
To assess if superior graft function (GFR difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.
Time frame: 1 year
1 secondary outcome
To compare the evolution of graft function (estimated GFR by means of modified MDRD formula)during the first 5 years post transplantation.
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2009.
- Derived from this study: PubMed 33277746Pipeleers L, Abramowicz D, Broeders N, Lemoine A, Peeters P, Van Laecke S, Weekers LE, Sennesael J, Wissing KM, Geers C, Bosmans JL. 5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients. Transpl Int. 2021 Feb;34(2):313-326. doi: 10.1111/tri.13798. Epub 2020 Dec 31.
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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.
Jean-Louis Bosmans, MD/PhD principal investigator
University Hospital Antwerp - Department Nephrology-Hypertension
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cyclosporine and Everolimus in people with Renal Transplantation, run by University Hospital, Antwerp at 5 sites in Belgium.
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 3 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 18 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Louis Bosmans, MD/PhD (+32/3/821 37 92, jeanlouis.bosmans@ua.ac.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess if superior graft function (GFR difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine. (time frame: 1 year). 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 NCT00903188, 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 18 May 2009.