SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus

NCT00371826 | Completed Phase 4 Results DMC

• 1 other identifier: CRAD001A2421
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Renal Transplanted Recipients

Keywords

Renal transplantation; everolimus; Immunosuppressants

Outcome Measures

Primary Outcomes (1)

• Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)

  The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.

  At Month 12

Secondary Outcomes (38)

• Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis)

  At Month 24 and 36

• Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (12 Months Analysis)

  At Month 12

• Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis)

  At Month 12, 24 and 36

• Number of Participants With Composite Endpoint of Treatment Failure (12 Months Analysis)

  Month 12

• Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis)

  At Month 12, 24 and 36

Study Arms (3)

Calcineurin Inhibitor (CNI) Withdrawal

EXPERIMENTAL

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

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

Steroid Withdrawal

EXPERIMENTAL

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

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

CNI+MPA+ Steroid

ACTIVE COMPARATOR

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.

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

Interventions

Everolimus (RAD001) DRUG

Also known as: Certican®

Calcineurin Inhibitor (CNI) Withdrawal; Steroid Withdrawal

Cyclosporine (Calcineurin Inhibitor (CNI)) DRUG

Also known as: Neoral®

CNI+MPA+ Steroid; Calcineurin Inhibitor (CNI) Withdrawal; Steroid Withdrawal

Methylprednisone/prednisone DRUG

CNI+MPA+ Steroid; Calcineurin Inhibitor (CNI) Withdrawal; Steroid Withdrawal

Mycophenolate sodium (MPA) DRUG

Also known as: myfortic®

CNI+MPA+ Steroid; Calcineurin Inhibitor (CNI) Withdrawal; Steroid Withdrawal

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.
• 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.
• Patients who have received an investigational drug within 4 weeks prior to the screening visit.
• Presence of any severe allergy or hypersensitivity to drugs similar to everolimus (e.g. antibiotics such as Clindamycin)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Royal Prince Alfred Hospital

NSW, Australia

Location

Westmead Hospital

NSW, Australia

Location

Princess Alexandra Hospital

QLD, Australia

Location

Monash Medical Centre

Sale, Australia

Location

Queen Elizabeth Hospital

Sale, Australia

Location

Royal Melbourne Hospital

VIC, Australia

Location

Sir Charles Gairdner Hospital

WA, Australia

Location

MeSH Terms

Interventions

Everolimus; Cyclosporine; Calcineurin Inhibitors; cni protein, Drosophila; Prednisone; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2006
• First Posted: September 4, 2006
• Study Start: March 1, 2006
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: August 19, 2013
• Results First Posted: August 19, 2013

Record last verified: 2013-06

Locations

AU (7)