Kidney TransplantationPhase 3EPARGNENCT00811915
Study to Compare the Safety and Efficacy of Sirolimus (Rapamune) to Tacrolimus (Advagraf) Associated to Mycophenolate Mofetil (CellCept) Between 12 and 36 Months After Kidney Transplantation
A Phase 3 study testing Sirolimus in people with Kidney Transplantation, run by University Hospital, Rouen at 8 sites in France.
Trial summary
The use of tacrolimus in the long term as part of the immunosuppressive regimen after transplantation is associated to complications such as chronic nephrotoxicity, impaired glucose metabolism (diabetes mellitus) and an increase of the incidence of neoplasia. Read more about this study
- Who is it for?
- Ages 18 to 76 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 8 sitesFrance
- Study dates
- Jan 2009to Jun 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 76 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipient age ≥18 and ≤ 75 ans.
- Patients having received a first or second renal transplant from a cadaveric or living related donor between 12 and 24 months prior the inclusion.
- Peak panel reactive antibody (PRA) < 30 %
- Patients with a stable renal function during the 3 months prior to inclusion (variation of serum creatinine lower than 20 %)
- Creatinine clearance ≥ 40 ml/mn/1.73 m26.
- Patients receiving as a stable immunosuppressive treatment associating: Mycophenolate mofetil (MPA AUC > 30 mg.h/L) and Tacrolimus with a trough level > 4 ng/ml, with or without corticoids
Who cannot join
- Multiorgan recipients
- Patients receiving cyclosporine
- Pregnancy
- Recipients of ABO incompatible graft
- Use of other immunosuppressive drugs.
- Historical peak reactive antibody ≥ 30 %
Show all 14Show fewer
- Past medical history of humoral rejection, 2 episodes of acute cellular rejection
- Past medical history of sub-clinical rejection on routine allograft biopsy
- Calculated creatinine clearance < 40 ml/mn/1.73 m2
- 24h proteinuria > 1 g/24H
- Patients with severe diarrhea
- HTLV1 or HIV positivity
- Known hypersensitivity to tacrolimus, mycophenolate mofetil, or sirolimus.
- Total white blood cells < 2500/mm3 or hemoglobin < 9 g/dl
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
UHAmiens
Amiens
UHAngers
Angers, 49933
UHCaen
Caen, 14000
UHLimoges
Limoges
UHNecker
Paris, 75015
UHRennes
Rennes, 35000
UHRouen
Rouen, 76000
UHTours
Tours
About this study
Official title: A Prospective, Comparative, Multicenter, Randomized Study to Compare the Safety and Efficacy of Sirolimus (Rapamune) to Tacrolimus (Advagraf) Associated to Mycophenolate Mofetil (CellCept) Between 12 and 36 Months After Kidney Transplantation
The use of tacrolimus in the long term as part of the immunosuppressive regimen after transplantation is associated to complications such as chronic nephrotoxicity, impaired glucose metabolism (diabetes mellitus) and an increase of the incidence of neoplasia. The conversion from a tacrolimus based therapy to a sirolimus based therapy associated with mycophenolate mofetil could improve the incidence of such complications. The aim of this study is to assess the risk/benefit ratio of this switch performed in stable renal transplant recipient between 12 months and 36 months after transplantation. The incidence of a composite endpoint (worsening of GFR evaluated by MDRD formula, incidence of cancer and diabetes) will be assessed 24 months after conversion.
Read the detailed description
Two doses of Sirolimus will be evaluated accorded to the CYP 3A5 genotype. Patients carrying at least CYP 3A5 *1 allele will receive 4 mg per day whereas the others (CYP 3A5 *3/*3) will receive 2 mg.
- Conditions
- Kidney Transplantation
- Being tested
- Sirolimus
- Keywords
- Sirolimus, Tacrolimus, Kidney transplantation, Kidney Transplant Recipients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Sirolimus introduction and tacrolimus withdrawal
Tacrolimus : 33 % decrease of daily dose with complete withdrawal at day 14. Sirolimus daily dose according to CYP3A5 genotype CYP3A5*1/*1 or *1/*3: 4 mg/d CYPY3A5*3/*3 : sirolimus 2 mg/j Adjusted to obtain a trough level between 6 and10 ng/ml
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Group A : Sirolimus introduction and tacrolimus withdrawal
* Tacrolimus : 33 % decrease of daily dose with complete withdrawal at day 14.
* Sirolimus daily dose according to CYP3A5 genotype CYP3A5*1/*1 or *1/*3: 4 mg/d CYPY3A5*3/*3 : sirolimus 2 mg/j Adjusted to obtain a trough level between 6 and10 ng/ml Receives: Drug: Sirolimus |
| B | Active comparator | Tacrolimus (Advagraf) dose to obtain a trough level between 4 and 10 ng/ml Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of a composite endpoint (worsening of GFR estimated with MDRD formula, incidence of cancer and incidence of post-transplant diabetes mellitus) will be assessed 24 months after conversion.
Measured: 24 months
Secondary outcomes (1)
*Renal function by calculated creatinine clearance* Incidence of biopsy proven acute rejection *Incidence of de novo diabetes mellitus *Incidence of hypertension *Incidence of skin cancer *Incidence of Chronic Rejection
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionDec 2013
- Study completionJun 2014
Why it stopped: Difficulty in enrolling new patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Isabelle ETIENNE, MD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811915
- Sponsor's protocol ID
- 2007/125/HP
- Acronym
- EPARGNE
- Status last verified
- Apr 2026
- First submitted
- 18 Dec 2008
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Comparative, Multicenter, Randomized Study to Compare the Safety and Efficacy of Sirolimus (Rapamune) to Tacrolimus (Advagraf) Associated to Mycophenolate Mofetil (CellCept) Between 12 and 36 Months After Kidney Transplantation
- ClinicalTrials.gov ID
- NCT00811915
- Acronym / sponsor ID
- EPARGNE / 2007/125/HP
- Conditions
- Kidney Transplantation
- Keywords
- Sirolimus, Tacrolimus, Kidney transplantation, Kidney Transplant Recipients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty in enrolling new patients
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 19 Dec 2008 (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 use of tacrolimus in the long term as part of the immunosuppressive regimen after transplantation is associated to complications such as chronic nephrotoxicity, impaired glucose metabolism (diabetes mellitus) and an increase of the incidence of neoplasia. The conversion from a tacrolimus based therapy to a sirolimus based therapy associated with mycophenolate mofetil could improve the incidence of such complications. The aim of this study is to assess the risk/benefit ratio of this switch performed in stable renal transplant recipient between 12 months and 36 months after transplantation. The incidence of a composite endpoint (worsening of GFR evaluated by MDRD formula, incidence of cancer and diabetes) will be assessed 24 months after conversion.
Detailed description
Two doses of Sirolimus will be evaluated accorded to the CYP 3A5 genotype. Patients carrying at least CYP 3A5 *1 allele will receive 4 mg per day whereas the others (CYP 3A5 *3/*3) will receive 2 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusGroup A : Sirolimus introduction and tacrolimus withdrawal * Tacrolimus : 33 % decrease of daily dose with complete withdrawal at day 14. * Sirolimus daily dose according to CYP3A5 genotype CYP3A5*1/*1 or *1/*3: 4 mg/d CYPY3A5*3/*3 : sirolimus 2 mg/j Adjusted to obtain a trough level between 6 and10 ng/ml |
| B | Active comparator | Drug: SirolimusTacrolimus (Advagraf) dose to obtain a trough level between 4 and 10 ng/ml |
Who may qualify
- Ages
- 18 to 76 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Recipient age ≥18 and ≤ 75 ans.
- Patients having received a first or second renal transplant from a cadaveric or living related donor between 12 and 24 months prior the inclusion.
- Peak panel reactive antibody (PRA) < 30 %
- Patients with a stable renal function during the 3 months prior to inclusion (variation of serum creatinine lower than 20 %)
- Creatinine clearance ≥ 40 ml/mn/1.73 m26.
Key exclusion criteria (14 listed)
- Multiorgan recipients
- Patients receiving cyclosporine
- Pregnancy
- Recipients of ABO incompatible graft
- Use of other immunosuppressive drugs.
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 |
|---|---|---|
| SirolimusSirolimus introduction and tacrolimus withdrawal Tacrolimus : 33 % decrease of daily dose with complete withdrawal at day 14. Sirolimus daily dose according to CYP3A5 genotype CYP3A5*1/*1 or *1/*3: 4 mg/d CYPY3A5*3/*3 : sirolimus 2 mg/j Adjusted to obtain a trough level between 6 and10 ng/ml | Drug | B, Sirolimus |
Primary outcome
The incidence of a composite endpoint (worsening of GFR estimated with MDRD formula, incidence of cancer and incidence of post-transplant diabetes mellitus) will be assessed 24 months after conversion.
Time frame: 24 months
1 secondary outcome
*Renal function by calculated creatinine clearance* Incidence of biopsy proven acute rejection *Incidence of de novo diabetes mellitus *Incidence of hypertension *Incidence of skin cancer *Incidence of Chronic Rejection
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Difficulty in enrolling new patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
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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.
Isabelle ETIENNE, MD principal investigator
University Hospital, Rouen
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Kidney Transplantation, run by University Hospital, Rouen at 8 sites in France.
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 14 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: stopped early, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. 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 was stopped early (reason given: Difficulty in enrolling new patients). Results are not available in the source record.
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?
The incidence of a composite endpoint (worsening of GFR estimated with MDRD formula, incidence of cancer and incidence of post-transplant diabetes mellitus) will be assessed 24 months after conversion. (time frame: 24 months). 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 14 Apr 2026.