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

Kidney Transplantation Clinical Trial

— EPARGNE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00811915
• Other study ID #: 2007/125/HP
• Status: Completed
• Phase: Phase 3
• First received: December 18, 2008
• Last updated: June 18, 2014
• Start date: January 2009
• Est. completion date: June 2014

Study information

• Verified date: June 2014
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: June 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 76 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Sirolimus
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

Locations

Country	Name	City	State
France	UHAmiens	Amiens
France	UHAngers	Angers
France	UHCaen	Caen
France	UHLimoges	Limoges
France	UHNecker	Paris
France	UHRennes	Rennes
France	UHRouen	Rouen
France	UHTours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	*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	No