Kidney Transplantation
Conditions
Keywords
Sirolimus, Tacrolimus, Kidney transplantation, Kidney Transplant Recipients
Brief 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. 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.
Interventions
DRUGSirolimus
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
Sponsors
University Hospital, Rouen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* Multiorgan recipients * Patients receiving cyclosporine * Pregnancy * Recipients of ABO incompatible graft * Use of other immunosuppressive drugs. * Historical peak reactive antibody ≥ 30 % * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| *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 | 24 months |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORIsabelle ETIENNE, MD
University Hospital, Rouen
Outcome results
None listed