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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01950819




Registration number
NCT01950819
Ethics application status
Date submitted
20/08/2013
Date registered
26/09/2013

Titles & IDs
Public title
Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)
Scientific title
A 24 Month, Multicenter, Randomized, Open-label Safety and Efficacy Study of Concentration-controlled Everolimus With Reduced Calcineurin Inhibitor vs Mycophenolate With Standard Calcineurin Inhibitor in de Novo Renal Transplantation
Secondary ID [1] 0 0
2013-000322-66
Secondary ID [2] 0 0
CRAD001A2433
Universal Trial Number (UTN)
Trial acronym
TRANSFORM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Renal Disease (ESRD) 0 0
Chronic Kidney Disease (CKD) 0 0
Hemodialysis 0 0
Renal Replacement Therapy 0 0
Renal Transplantation 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Induction therapy
Treatment: Drugs - Corticosteroids
Treatment: Drugs - EVR+rCNI
Treatment: Drugs - MPA+sCNI

Experimental: EVR+rCNI - Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)

Active comparator: MPA+sCNI - Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).


Treatment: Other: Induction therapy
All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.

Treatment: Drugs: Corticosteroids
All subjects received maintenance therapy with corticosteroids throughout the 24 month study period. A minimum dose of 5 mg prednisone, or equivalent, per day was maintained.

Treatment: Drugs: EVR+rCNI
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)

Treatment: Drugs: MPA+sCNI
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2.
Timepoint [1] 0 0
Month 12 is Primary, Month 24 secondary
Secondary outcome [1] 0 0
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death
Timepoint [1] 0 0
Month 12 and 24
Secondary outcome [2] 0 0
Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2
Timepoint [2] 0 0
Month 12 and 24
Secondary outcome [3] 0 0
Incidence of Failure on the Composite Endpoint of Graft Loss or Death.
Timepoint [3] 0 0
Month 12 and 24
Secondary outcome [4] 0 0
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection
Timepoint [4] 0 0
Month 12 and 24
Secondary outcome [5] 0 0
Incidence of eGFR < 50 mL/Min/1.73m2
Timepoint [5] 0 0
Month 12 and 24
Secondary outcome [6] 0 0
Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR
Timepoint [6] 0 0
Baseline (week 4), Month 12 and 24
Secondary outcome [7] 0 0
Evolution of Renal Function, as eGFR, Over Time by Slope Analysis.
Timepoint [7] 0 0
Month 12 and 24
Secondary outcome [8] 0 0
Renal Function Assessed by Creatinine Lab Values
Timepoint [8] 0 0
Month 12 and 24
Secondary outcome [9] 0 0
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported
Timepoint [9] 0 0
Month 12 and 24
Secondary outcome [10] 0 0
Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation.
Timepoint [10] 0 0
Month 24
Secondary outcome [11] 0 0
Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events.
Timepoint [11] 0 0
Month 24
Secondary outcome [12] 0 0
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios.
Timepoint [12] 0 0
Baseline, Month 12 and 24
Secondary outcome [13] 0 0
Incidence of Major Cardiovascular Events.
Timepoint [13] 0 0
Month 24
Secondary outcome [14] 0 0
Incidence of Malignancies.
Timepoint [14] 0 0
Month 24
Secondary outcome [15] 0 0
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects.
Timepoint [15] 0 0
Month 12 and 24
Secondary outcome [16] 0 0
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants)
Timepoint [16] 0 0
Month 12 and 24
Secondary outcome [17] 0 0
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events)
Timepoint [17] 0 0
Month 12 and 24
Secondary outcome [18] 0 0
Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections
Timepoint [18] 0 0
Month 12 and 24
Secondary outcome [19] 0 0
Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup
Timepoint [19] 0 0
Month 12 and 24
Secondary outcome [20] 0 0
Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2
Timepoint [20] 0 0
Month 12 and 24
Secondary outcome [21] 0 0
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up
Timepoint [21] 0 0
Month 12 and 24

Eligibility
Key inclusion criteria
1. Written informed consent obtained.
2. Subject randomized within 24 hr of completion of transplant surgery.
3. Recipient of a kidney with a cold ischemia time < 30 hours.
4. Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject unable to tolerate oral medication at time of randomization.
2. Use of other investigational drugs at the time of enrollment.
3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
4. Multi-organ transplant recipient.
5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
6. Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.
7. Subject who is HIV-positive.
8. HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels = 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable.
9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).
10. Subject with a BMI greater than 35.
11. Subject with severe systemic infections, current or within the two weeks prior to randomization.
12. Subject requiring systemic anticoagulation.
13. History of malignancy of any organ system.
14. Subject with severe restrictive or obstructive pulmonary disorders.
15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.
16. Subject with white blood cell (WBC) count = 2,000 /mm3 or with platelet count = 50,000 /mm3.
17. Pregnant or nursing (lactating) women.
18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

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
3/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/01/2018
Sample size
Target
Accrual to date
Final
2037
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [3] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [4] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [5] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [6] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [7] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [8] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [9] 0 0
Novartis Investigative Site - Murdoch
Recruitment hospital [10] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3050 - Parkville
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
California
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Colorado
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Illinois
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Maryland
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Massachusetts
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Michigan
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Missouri
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New Jersey
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North Carolina
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Washington
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Wisconsin
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Argentina
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Buenos Aires
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Santa Fe
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Tyrol
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Linz
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Brno
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BO
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MI
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PD
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PR
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Italy
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RM
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SI
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TO
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Jalisco
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Singapore
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Kosice
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Martin
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Ljubljana
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Andalucia
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Barcelona
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Cantabria
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Santa Cruz De Tenerife
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Spain
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Madrid
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Zaragoza
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Sweden
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Göteborg
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Sweden
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Stockholm
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Sweden
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Uppsala
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Switzerland
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Bern
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Taiwan
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Taiwan ROC
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Taichung
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Taiwan
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Taipei
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Thailand
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Bangkok
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Turkey
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Antalya
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Istanbul
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Turkey
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Mecidiyekoy/Istanbul

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 Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydata request.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01950819