SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus

Novartis

Status and phase: Completed; Phase 4

Conditions: Renal Transplanted Recipients

Treatments: Drug: Methylprednisone/prednisone; Drug: Cyclosporine (Calcineurin Inhibitor (CNI)); Drug: Mycophenolate sodium (MPA); Drug: Everolimus (RAD001)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00371826

CRAD001A2421

Details and patient eligibility

About

The aim of this study is to assess the safety and efficacy of corticosteroid discontinuation versus cyclosporine micro emulsion discontinuation in recipients receiving reduced exposure cyclosporine micro emulsion and corticosteroids plus enteric-coated mycophenolate sodium (EC-MPS) initially, changed to everolimus at 2 weeks post-transplant. These two groups will be compared to a third control group, who will receive treatment consisting of cyclosporine micro emulsion, enteric-coated mycophenolate sodium (EC-MPS) and steroids.

Enrollment: 126 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

1. Males and females aged 18-65 years inclusive.
2. First time recipients of cadaveric, living unrelated or living related donor kidney transplants.
3. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.

Exclusion criteria

1. Patients who are recipients of multiple organ transplants, including more than one kidney, kidney and pancreas, or previous transplant with any organ other than kidney.
2. Patients at high immunological risk of graft loss, indicated by peak PRA >50% or loss of a previous renal allograft within the first 6 months of transplantation due to acute rejection.
3. Patients who have received an investigational drug within 4 weeks prior to the screening visit.
4. Presence of any severe allergy or hypersensitivity to drugs similar to everolimus (e.g. antibiotics such as Clindamycin)

Other protocol-defined inclusion/exclusion criteria may applied

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 3 patient groups

Calcineurin Inhibitor (CNI) Withdrawal

Experimental group

Description:

Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day

Treatment:

Drug: Mycophenolate sodium (MPA)

Drug: Everolimus (RAD001)

Drug: Methylprednisone/prednisone

Drug: Cyclosporine (Calcineurin Inhibitor (CNI))

Steroid Withdrawal

Experimental group

Description:

Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol

Treatment:

Drug: Mycophenolate sodium (MPA)

Drug: Everolimus (RAD001)

Drug: Methylprednisone/prednisone

Drug: Cyclosporine (Calcineurin Inhibitor (CNI))

CNI+MPA+ Steroid

Active Comparator group

Description:

Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.

Treatment:

Drug: Mycophenolate sodium (MPA)

Drug: Methylprednisone/prednisone

Drug: Cyclosporine (Calcineurin Inhibitor (CNI))