EVEROLD: mTor-inhibitor (EVERolimus) Based Immunosuppressive Strategies for CNI Minimisation in OLD for Old Renal Transplantation

Sponsor

University Hospital, Brest (Other)

Overall Status

Completed

CT.gov ID

NCT01028092

Collaborator

Novartis (Industry), Roche Pharma AG (Industry), Genzyme, a Sanofi Company (Industry), Ministry of Health, France (Other)

327

Enrollment

Locations

Arms

Duration (Months)

18.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate efficacity and safety of everolimus or (cyclosporine then everolimus) vs. cyclosporine as immunosuppressive treatment in renal transplantation for elderly (>60 years old) recipients receiving graft from elderly donor(>60 years old).

Condition or Disease	Intervention/Treatment	Phase
Renal Transplant	Drug: Anti R-IL2 + Cyclosporine Drug: Thymoglobulin + Everolimus Drug: Anti R-IL2 + Cyclosporine then Everolimus	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

327 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

mTor-inhibitor (EVERolimus) Based Immunosuppressive Strategies for CNI Minimisation in OLD for Old Renal Transplantation

Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control anti R-IL2 induction + Mycophenolate Mofetil + cyclosporine A + corticosteroids	Drug: Anti R-IL2 + Cyclosporine anti R-IL2 induction (Simulect ®, 20 mg D0 and D4) Mycophenolate Mofetil (Cellcept ®) 3 grams per day beginning at D0 cyclosporine A (Neoral ®) started from 6 to 8 mg/kg adjusted to C2 corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6
Experimental: CNI-free Thymoglobulin + Mycophenolate Mofetil + everolimus + corticosteroids	Drug: Thymoglobulin + Everolimus Thymoglobulin ® induction started at 1.5mg/kg/j then adjusted to CD2 or total lymphocytes count, for 5 days Mycophenolate Mofetil (Cellcept ®) 3 grams per day beginning at D0 everolimus (Certican ®): 4 to 6 mg/day started at D5, adjusted to achieve a residual level between 6 et 10 ng/ml corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6
Experimental: Switch anti R-IL2 + Mycophenolate Mofetil + (Cyclosporine then Everolimus) + corticosteroids	Drug: Anti R-IL2 + Cyclosporine then Everolimus anti R-IL2 induction (Simulect ®, 20 mg D0 and D4) Mycophenolate Mofetil (Cellcept ®) 3 g/d beginning at D0 cyclosporine A (Neoral ®) beginning at 6 to 8 mg/kg adjusted to C2, then switch to everolimus (Certican ®) between at W6, started at 3 mg/d, then adjusted to achieve a residual level between 6 et 10 ng/ml corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6

Arm

Intervention/Treatment

Active Comparator: Control

anti R-IL2 induction + Mycophenolate Mofetil + cyclosporine A + corticosteroids

Drug: Anti R-IL2 + Cyclosporine

anti R-IL2 induction (Simulect ®, 20 mg D0 and D4) Mycophenolate Mofetil (Cellcept ®) 3 grams per day beginning at D0 cyclosporine A (Neoral ®) started from 6 to 8 mg/kg adjusted to C2 corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6

Experimental: CNI-free

Thymoglobulin + Mycophenolate Mofetil + everolimus + corticosteroids

Drug: Thymoglobulin + Everolimus

Thymoglobulin ® induction started at 1.5mg/kg/j then adjusted to CD2 or total lymphocytes count, for 5 days Mycophenolate Mofetil (Cellcept ®) 3 grams per day beginning at D0 everolimus (Certican ®): 4 to 6 mg/day started at D5, adjusted to achieve a residual level between 6 et 10 ng/ml corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6

Experimental: Switch

anti R-IL2 + Mycophenolate Mofetil + (Cyclosporine then Everolimus) + corticosteroids

Drug: Anti R-IL2 + Cyclosporine then Everolimus

anti R-IL2 induction (Simulect ®, 20 mg D0 and D4) Mycophenolate Mofetil (Cellcept ®) 3 g/d beginning at D0 cyclosporine A (Neoral ®) beginning at 6 to 8 mg/kg adjusted to C2, then switch to everolimus (Certican ®) between at W6, started at 3 mg/d, then adjusted to achieve a residual level between 6 et 10 ng/ml corticosteroids 250 mg IV before and after surgery, then 1 mg/kg one week and 20mg/j the week after, then tapered until 10 mg/j at M1, 5 mg at M3 and stop between M4 and M6

Outcome Measures

Primary Outcome Measures

calculated renal function with MDRD equation [12 months]

Secondary Outcome Measures

Acute rejection rate [12 months]
Patient and graft survival rate [12 months]
Adverse events [12 months]
GFR calculated with Cockcroft Gault formula [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient who has given written informed consent to participate in the study
First or second single transplantation of a recipient (male or female) older than 60 years old
Donor older than 60 years old
PRA < 30%

Exclusion Criteria:

Living donor
Third transplantation
PRA > 30%

Other protocol-defined inclusion/exclusion criteria may apply.

Recipient of multi-organ transplant
Active major infections (HBV, HCV, HIV)
Loss of a first graft for immunologic issues
Anemia (<9g/l) or leucopenia (<2500/mm3)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Amiens	Amiens	France
2	CHU Pellegrin - Bordeaux	Bordeaux	France
3	CHRU de BREST	Brest	France	29609
4	CHU Cote de Nacre	Caen	France
5	CHU Clermont Ferrand	Clermont Ferrand	France
6	CHU Dijon	Dijon	France
7	CHU Lille	Lille	France
8	CHU Limoges	Limoges	France
9	CHU Montpellier	Montpellier	France
10	CHU Nice	Nice	France
11	AP-HP Hopital Necker	Paris	France
12	CHU Poitiers	Poitiers	France
13	CHU Reims	Reims	France
14	CHU Rennes	Rennes	France
15	CHU Rouen	Rouen	France
16	Hopitaux Universitaires de Strasbourg	Strasbourg	France
17	CHU Rangueil - Toulouse	Toulouse	France
18	CHU Tours	Tours	France