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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00371826




Registration number
NCT00371826
Ethics application status
Date submitted
1/09/2006
Date registered
4/09/2006
Date last updated
19/08/2013

Titles & IDs
Public title
SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus
Scientific title
A Prospective, Open-label, Controlled Multicenter Trial to Assess the Efficacy and Safety of an Induction Regimen of Cyclosporine Micro Emulsion, Enteric-coated Mycophenolate Sodium (EC-MPS) and Corticosteroids, Followed by Administration of Everolimus and Enteric-coated Mycophenolate Sodium (EC-MPS), With Either the Withdrawal of Cyclosporine Micro Emulsion or Corticosteroids in de Novo Kidney Transplant Recipients
Secondary ID [1] 0 0
CRAD001A2421
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Transplanted Recipients 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Calcineurin Inhibitor (CNI) Withdrawal - 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

Experimental: Steroid Withdrawal - 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

Active comparator: CNI+MPA+ Steroid - 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.

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)
Timepoint [1] 0 0
At Month 12
Secondary outcome [1] 0 0
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis)
Timepoint [1] 0 0
At Month 24 and 36
Secondary outcome [2] 0 0
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (12 Months Analysis)
Timepoint [2] 0 0
At Month 12
Secondary outcome [3] 0 0
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis)
Timepoint [3] 0 0
At Month 12, 24 and 36
Secondary outcome [4] 0 0
Number of Participants With Composite Endpoint of Treatment Failure (12 Months Analysis)
Timepoint [4] 0 0
Month 12
Secondary outcome [5] 0 0
Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis)
Timepoint [5] 0 0
At Month 12, 24 and 36
Secondary outcome [6] 0 0
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis)
Timepoint [6] 0 0
At Month 12
Secondary outcome [7] 0 0
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis)
Timepoint [7] 0 0
At Month 36
Secondary outcome [8] 0 0
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis)
Timepoint [8] 0 0
At Month 12
Secondary outcome [9] 0 0
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis)
Timepoint [9] 0 0
At Month 36
Secondary outcome [10] 0 0
Mean Serum Creatinine (12 Months Analysis)
Timepoint [10] 0 0
At Month 12
Secondary outcome [11] 0 0
Mean Serum Creatinine (36 Months Analysis)
Timepoint [11] 0 0
At Month 12, 18, 24 and 36
Secondary outcome [12] 0 0
Creatinine Clearance (CrCl) Calculated by the Cockcroft-Gault Formula (12 Months Analysis)
Timepoint [12] 0 0
At Month 12
Secondary outcome [13] 0 0
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis)
Timepoint [13] 0 0
At Month 12, 24 and 36
Secondary outcome [14] 0 0
Mean Urine Albumin/Creatinine Ratio (ACR) as Measurement of Proteinuria (12 Months Analysis)
Timepoint [14] 0 0
At Month 12
Secondary outcome [15] 0 0
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis)
Timepoint [15] 0 0
At Month 12, 18, 24 and 36
Secondary outcome [16] 0 0
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis)
Timepoint [16] 0 0
At Month 12
Secondary outcome [17] 0 0
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis)
Timepoint [17] 0 0
At Month 36
Secondary outcome [18] 0 0
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)
Timepoint [18] 0 0
Baseline, Overall post-baseline up to 12 month
Secondary outcome [19] 0 0
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)
Timepoint [19] 0 0
Baseline, Overall post baseline up to Month 36
Secondary outcome [20] 0 0
Number of Participants With Erythropoietin Usage (12 Months Analysis)
Timepoint [20] 0 0
Month 12
Secondary outcome [21] 0 0
Number of Participants With Erythropoietin Usage (36 Months Analysis)
Timepoint [21] 0 0
Month 36
Secondary outcome [22] 0 0
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis)
Timepoint [22] 0 0
At Month 12
Secondary outcome [23] 0 0
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis)
Timepoint [23] 0 0
At Month 24
Secondary outcome [24] 0 0
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (12 Months Analysis)
Timepoint [24] 0 0
Month 12
Secondary outcome [25] 0 0
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (36 Months Analysis)
Timepoint [25] 0 0
Month 36
Secondary outcome [26] 0 0
Number of Participants With Employment Status (12 Months Analysis)
Timepoint [26] 0 0
At screening (at day 0 +/- 7 days ), At Month 12
Secondary outcome [27] 0 0
Number of Participants With Employment Status (36 Months Analysis)
Timepoint [27] 0 0
At screening (at day 0 +/- 7 days ), At Month 36
Secondary outcome [28] 0 0
Number of Participants With Wound Problems(12 Months Analysis)
Timepoint [28] 0 0
At Month 12
Secondary outcome [29] 0 0
Number of Participants With Any Wound Problems (36 Months Analysis)
Timepoint [29] 0 0
At Month 12, 24 and 36
Secondary outcome [30] 0 0
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)
Timepoint [30] 0 0
Overall post baseline up to month 12
Secondary outcome [31] 0 0
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)
Timepoint [31] 0 0
Overall Post Baseline up to month 36
Secondary outcome [32] 0 0
Number of Participants With Antibody-mediated Rejection Per Treatment Group (12 Months Analysis)
Timepoint [32] 0 0
At Month 12
Secondary outcome [33] 0 0
Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis)
Timepoint [33] 0 0
At Month 12, 24 and 36
Secondary outcome [34] 0 0
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis)
Timepoint [34] 0 0
At Month 12
Secondary outcome [35] 0 0
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis)
Timepoint [35] 0 0
At Month 36
Secondary outcome [36] 0 0
Number of Patient Survival and Graft Survival (12 Months Analysis)
Timepoint [36] 0 0
At Month 12
Secondary outcome [37] 0 0
Number of Patient Survival and Graft Survival (36 Months Analysis)
Timepoint [37] 0 0
At Month 12, 24 and 36
Secondary outcome [38] 0 0
Change in Bone Mineral Density Between Week 2 and Month 24 (36 Months Analysis)
Timepoint [38] 0 0
Week 2, Month 24

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - NSW
Recruitment hospital [2] 0 0
Westmead Hospital - NSW
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - QLD
Recruitment hospital [4] 0 0
Monash Medical Centre - Sale
Recruitment hospital [5] 0 0
Queen Elizabeth Hospital - Sale
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - VIC
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - WA
Recruitment postcode(s) [1] 0 0
- NSW
Recruitment postcode(s) [2] 0 0
- QLD
Recruitment postcode(s) [3] 0 0
- Sale
Recruitment postcode(s) [4] 0 0
- VIC
Recruitment postcode(s) [5] 0 0
- WA

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis
Address 0 0
Novartis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.