Study to Compare the Safety and Efficacy of Sirolimus (Rapamune) to Tacrolimus (Advagraf) Associated to Mycophenolate Mofetil (CellCept) Between 12 and 24 Months After Kidney Transplantation - Full Text View

Sponsored by:	University Hospital, Rouen
Information provided by:	University Hospital, Rouen
ClinicalTrials.gov Identifier:	NCT00811915

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 24 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 III

MedlinePlus related topics: Cancer Diabetes Kidney Transplantation

Drug Information available for: Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Sirolimus Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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 24 Months After Kidney Transplantation

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:	December 2012
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sirolimus: Experimental 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 CYP3A51/1 or 1/3: 4 mg/d CYPY3A53/3 : 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 CYP3A51/1 or 1/3: 4 mg/d CYPY3A53/3 : sirolimus 2 mg/j Adjusted to obtain a trough level between 6 and10 ng/ml
B: Active Comparator 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 CYP3A51/1 or 1/3: 4 mg/d CYPY3A53/3 : 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:

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 hypersentivity 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

Contacts

Contact: BARBIER Stephane, PhD

0232889152

Stephane.barbier@chu-rouen.fr

Sponsors and Collaborators

University Hospital, Rouen

Investigators

Principal Investigator:

BARBIER Stephane, PhD

University Hospital, Rouen

More Information

Responsible Party:	University Hospital, Rouen ( University Hospital, Rouen )
Study ID Numbers:	2007/125/HP
Study First Received:	December 18, 2008
Last Updated:	December 18, 2008
ClinicalTrials.gov Identifier:	NCT00811915
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by University Hospital, Rouen:

Sirolimus
Tacrolimus
Kidney transplantation
Kidney Tranplant Recipients

Study placed in the following topic categories:

Sirolimus
Clotrimazole
Miconazole

Tioconazole
Mycophenolate mofetil
Tacrolimus

Additional relevant MeSH terms:

Anti-Bacterial Agents
Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Antifungal Agents

Therapeutic Uses
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009