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 (EPARGNE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT00811915
First received: December 18, 2008
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Kidney Transplantation
Drug: Sirolimus
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Rouen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • *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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: December 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus

Groupe 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
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

Active Comparator: B
Tacrolimus (Advagraf) dose to obtain a trough level between 4 and 10 ng/ml
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


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

Ages Eligible for Study:   18 Years to 76 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 mofétil (MPA AUC > 30 mg.h/L) and Tacrolimus with a trough level > 4 ng/ml, with or without corticoids

Exclusion Criteria:

  • Multi-organ 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, mycophénolate mofétil, or sirolimus.
  • Total white blood cells < 2500/mm3 or hemoglobine < 9 g/dl
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00811915

Locations
France
UHAmiens
Amiens, France
UHAngers
Angers, France, 49933
UHCaen
Caen, France, 14000
UHLimoges
Limoges, France
UHNecker
Paris, France, 75015
UHRennes
Rennes, France, 35000
UHRouen
Rouen, France, 76000
UHTours
Tours, France
Sponsors and Collaborators
University Hospital, Rouen
Investigators
Principal Investigator: Isabelle ETIENNE, MD University Hospital, Rouen
  More Information

No publications provided

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT00811915     History of Changes
Other Study ID Numbers: 2007/125/HP
Study First Received: December 18, 2008
Last Updated: January 10, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Rouen:
Sirolimus
Tacrolimus
Kidney transplantation
Kidney Transplant Recipients

Additional relevant MeSH terms:
Mycophenolate mofetil
Sirolimus
Everolimus
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 16, 2014