Clinical trial NCT00811915: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Transplantation
Keywords: Sirolimus
Tacrolimus
Kidney transplantation
Kidney Transplant Recipients
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2008-12-19
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
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.
timeFrame: 24 months
Secondary outcomes:
measure: *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
timeFrame: 24 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: UHAmiens
city: Angers
country: France
facility: UHAngers
city: Caen
country: France
facility: UHCaen
city: Limoges
country: France
facility: UHLimoges
city: Paris
country: France
facility: UHNecker
city: Rennes
country: France
facility: UHRennes
city: Rouen
country: France
facility: UHRouen
city: Tours
country: France
facility: UHTours
Study officials:
affiliation: University Hospital, Rouen
name: Isabelle ETIENNE, MD
role: PRINCIPAL_INVESTIGATOR
References: