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

NCT00811915 | Terminated Phase 3

• 1 other identifier: 2007/125/HP
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 8

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.

Conditions

Kidney Transplantation

Keywords

Sirolimus; Tacrolimus; Kidney transplantation; Kidney Transplant Recipients

Outcome Measures

Primary Outcomes (1)

• 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 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

  24 months

Study Arms (2)

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

Drug: Sirolimus

B

ACTIVE COMPARATOR

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

Drug: Sirolimus

Interventions

Sirolimus DRUG

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; Sirolimus

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient age ≥18 and ≤ 75 ans.
• Peak panel reactive antibody (PRA) \< 30 %
• 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

You may not qualify if:

• 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
• h 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

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (8)

UHAmiens

Amiens, France

Location

UHAngers

Angers, 49933, France

Location

UHCaen

Caen, 14000, France

Location

UHLimoges

Limoges, France

Location

UHNecker

Paris, 75015, France

Location

UHRennes

Rennes, 35000, France

Location

UHRouen

Rouen, 76000, France

Location

UHTours

Tours, France

Location

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Isabelle ETIENNE, MD

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

FR (8)