Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)
TRANSFORM
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
2 other identifiers
interventional
2,037
39 countries
167
Brief Summary
This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Dec 2013
Longer than P75 for phase_4
167 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 20, 2013
CompletedFirst Posted
Study publicly available on registry
September 26, 2013
CompletedStudy Start
First participant enrolled
December 3, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 17, 2018
CompletedResults Posted
Study results publicly available
January 30, 2019
CompletedJanuary 30, 2019
January 1, 2019
3.2 years
August 20, 2013
October 3, 2018
January 9, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2.
Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2.
Month 12 is Primary, Month 24 secondary
Secondary Outcomes (21)
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death
Month 12 and 24
Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2
Month 12 and 24
Incidence of Failure on the Composite Endpoint of Graft Loss or Death.
Month 12 and 24
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection
Month 12 and 24
Incidence of eGFR < 50 mL/Min/1.73m2
Month 12 and 24
- +16 more secondary outcomes
Study Arms (2)
EVR+rCNI
EXPERIMENTALEverolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
MPA+sCNI
ACTIVE COMPARATORMycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Interventions
All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.
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.
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Eligibility Criteria
You may qualify if:
- Written informed consent obtained.
- Subject randomized within 24 hr of completion of transplant surgery.
- Recipient of a kidney with a cold ischemia time \< 30 hours.
- 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.
You may not qualify if:
- Subject unable to tolerate oral medication at time of randomization.
- Use of other investigational drugs at the time of enrollment.
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- Multi-organ transplant recipient.
- Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
- 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.
- Subject who is HIV-positive.
- 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.
- 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).
- Subject with a BMI greater than 35.
- Subject with severe systemic infections, current or within the two weeks prior to randomization.
- Subject requiring systemic anticoagulation.
- History of malignancy of any organ system.
- Subject with severe restrictive or obstructive pulmonary disorders.
- Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (184)
Novartis Investigative Site
Birmingham, Alabama, 35233, United States
Novartis Investigative Site
Loma Linda, California, 92354, United States
Novartis Investigative Site
Los Angeles, California, 90033, United States
Novartis Investigative Site
Los Angeles, California, 90048, United States
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Sacramento, California, 95817-1460, United States
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San Diego, California, 92123, United States
Novartis Investigative Site
San Francisco, California, 94115, United States
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San Francisco, California, 94143-0116, United States
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Aurora, Colorado, 80045, United States
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Denver, Colorado, 80210, United States
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Chicago, Illinois, 60612, United States
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Baltimore, Maryland, 21201, United States
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Boston, Massachusetts, 02114, United States
Novartis Investigative Site
Boston, Massachusetts, 02215, United States
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Burlington, Massachusetts, 01805, United States
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Ann Arbor, Michigan, 48109-0331, United States
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Detroit, Michigan, 48202, United States
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St Louis, Missouri, 63110, United States
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Livingston, New Jersey, 07039, United States
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Buffalo, New York, 14215, United States
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The Bronx, New York, 10467, United States
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Chapel Hill, North Carolina, 27599, United States
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Durham, North Carolina, 27710, United States
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Winston-Salem, North Carolina, 27157, United States
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Cleveland, Ohio, 44106-5048, United States
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Cleveland, Ohio, 44195, United States
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Columbus, Ohio, 43210, United States
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Harrisburg, Pennsylvania, 17105-8700, United States
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Providence, Rhode Island, 02903, United States
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Charleston, South Carolina, 29425, United States
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Nashville, Tennessee, 37212-3139, United States
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Dallas, Texas, 75246, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030-2400, United States
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Houston, Texas, 77030, United States
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Salt Lake City, Utah, 84132, United States
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Charlottesville, Virginia, 22908, United States
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Seattle, Washington, 98195, United States
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Madison, Wisconsin, 53705, United States
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Milwaukee, Wisconsin, 53226, United States
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CABA, Buenos Aires, C1181ACH, Argentina
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San Martín, Buenos Aires, C1107BEA, Argentina
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Buenos Aires, W3400ABH, Argentina
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Corrientes, W3400, Argentina
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Córdoba, X5016KEH, Argentina
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Córdoba, X5016KET, Argentina
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Santa Fe, S3000EPV, Argentina
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Camperdown, New South Wales, 2050, Australia
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Randwick, New South Wales, 2031, Australia
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Westmead, New South Wales, 2145, Australia
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Woolloongabba, Queensland, 4102, Australia
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Adelaide, South Australia, 5000, Australia
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Clayton, Victoria, 3168, Australia
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Heidelberg, Victoria, 3084, Australia
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Parkville, Victoria, 3050, Australia
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Murdoch, Western Australia, 6150, Australia
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Nedlands, Western Australia, 6009, Australia
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Innsbruck, Tyrol, 6020, Austria
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Linz, A-4010, Austria
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Edegem, Antwerpen, 2650, Belgium
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Brussels, 1070, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Porto Alegre, Rio Grande do Sul, 90020-090, Brazil
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São Paulo, São Paulo, 04038-002, Brazil
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São Paulo, São Paulo, 05403 000, Brazil
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Sofia, BGR, 1431, Bulgaria
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Santiago, 8207257, Chile
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Cali, Valle del Cauca Department, Colombia
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Bogotá, Colombia
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Rijeka, 51000, Croatia
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Zagreb, 10000, Croatia
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Zagreb, 1000, Croatia
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Brno, 656 91, Czechia
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Prague, 140 00, Czechia
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Al Mansurah, Egypt
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Nice, Cedex1, 06001, France
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Tours, Indre Et Loire, 37044, France
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Montpellier, 34295, France
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Paris, 75015, France
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Reims, 51092, France
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Regensburg, Bavaria, 93053, Germany
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Berlin, 12203, Germany
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Berlin, 13353, Germany
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Cologne, 51109, Germany
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Essen, 45147, Germany
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Hannover Muenden, 34346, Germany
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Hanover, 30625, Germany
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Heidelberg, 69120, Germany
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Kaiserslautern, 67655, Germany
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Leipzig, 04103, Germany
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München, 81377, Germany
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München, 81675, Germany
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Thessaloniki, GR, 546 42, Greece
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Athens, 106 76, Greece
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Athens, 11527, Greece
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Pátrai, 265 00, Greece
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Bangalore, Karnataka, 560 055, India
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Mumbai, Maharashtra, 400 016, India
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New Delhi, National Capital Territory of Delhi, 110 017, India
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Vellore, Tamil Nadu, 632004, India
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Petah Tikva, 49100, Israel
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Tel Aviv, 64239, Israel
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Bari, BA, 70124, Italy
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Bologna, BO, 40138, Italy
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Milan, MI, 20162, Italy
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Padua, PD, 35128, Italy
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Parma, PR, 43100, Italy
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Roma, RM, 00144, Italy
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Roma, RM, 00168, Italy
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Siena, SI, 53100, Italy
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Torino, TO, 10126, Italy
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Novara, 28100, Italy
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Nagoya, Aichi-ken, 466-8650, Japan
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Toyoake, Aichi-ken, 470 1192, Japan
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Chiba, Chiba, 260-8712, Japan
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Kuwait City, Kuwait
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El Achrafiyé, 166830, Lebanon
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Saida, 652, Lebanon
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Saida, Lebanon
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Kuala Lumpur, 50589, Malaysia
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Selangor Darul Ehsan, 68100, Malaysia
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Guadalajara, Jalisco, 44610, Mexico
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Maastricht, AZ, 5800, Netherlands
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Utrecht, The Netherlands, 3508 GA, Netherlands
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Amsterdam, 1105 AZ, Netherlands
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Groningen, Netherlands
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Leiden, 2333 ZA, Netherlands
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Nijmegen, Netherlands
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Oslo, 0424, Norway
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Quezon City, 1101, Philippines
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Szczecin, Pomeranian Voivodeship, 70-111, Poland
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Gdansk, 80 952, Poland
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Poznan, 60-355, Poland
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Poznan, 60-479, Poland
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Carnaxide, Lisbon District, 2790-134, Portugal
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Coimbra, 3000 075, Portugal
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Lisbon, 1069-166, Portugal
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Lisbon, 1600190, Portugal
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Porto, 4200 319, Portugal
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Krasnodar, 350086, Russia
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Moscow, 123182, Russia
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Moscow, 129010, Russia
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Nizhny Novgorod, 603000, Russia
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Volzhskiy, 404120, Russia
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Yekaterinburg, 620109, Russia
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Dammam, 15215, Saudi Arabia
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Jeddah, 21499, Saudi Arabia
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Riyadh, 11159, Saudi Arabia
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Belgrade, 11000, Serbia
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Niš, 18000, Serbia
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Novi Sad, Serbia
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Singapore, 169608, Singapore
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Banská Bystrica, 97517, Slovakia
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Bratislava, 833 05, Slovakia
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Košice, 04166, Slovakia
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Martin, 03659, Slovakia
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Ljubljana, 1000, Slovenia
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Cape Town, Western Province, 7925, South Africa
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Seoul, Korea, 05505, South Korea
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Seoul, Korea, 06351, South Korea
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Seoul, 03722, South Korea
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Granada, Andalusia, 18014, Spain
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Santander, Cantabria, 39008, Spain
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Barcelona, Catalonia, 08003, Spain
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Barcelona, Catalonia, 08036, Spain
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San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain
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Valencia, Valencia, 46017, Spain
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Madrid, 28034, Spain
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Madrid, 28041, Spain
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Zaragoza, 50009, Spain
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Gothenburg, SE-413 45, Sweden
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Stockholm, 14186, Sweden
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Uppsala, 751 85, Sweden
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Bern, 3010, Switzerland
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Tainan, Taiwan ROC, 70421, Taiwan
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Taichung, 40705, Taiwan
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Taipei, 10002, Taiwan
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Ratchathewi, Bangkok, 10400, Thailand
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Bangkok, 10400, Thailand
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Antalya, 07070, Turkey (Türkiye)
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Istanbul, 34093, Turkey (Türkiye)
Novartis Investigative Site
Mecidiyekoy/Istanbul, 34394, Turkey (Türkiye)
Related Publications (5)
Aubert O, Divard G, Pascual J, Oppenheimer F, Sommerer C, Citterio F, Tedesco H, Chadban S, Henry M, Vincenti F, Srinivas T, Watarai Y, Legendre C, Bernhardt P, Loupy A. Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial: proof-of-concept study. BMJ Open. 2021 Oct 7;11(10):e052138. doi: 10.1136/bmjopen-2021-052138.
PMID: 34620664DERIVEDWatarai Y, Danguilan R, Casasola C, Chang SS, Ruangkanchanasetr P, Kee T, Wong HS, Kenmochi T, Amante AJ, Shu KH, Ingsathit A, Bernhardt P, Hernandez-Gutierrez MP, Han DJ, Kim MS. Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study. Clin Transplant. 2021 Oct;35(10):e14415. doi: 10.1111/ctr.14415. Epub 2021 Sep 23.
PMID: 34216395DERIVEDCitterio F, Henry M, Kim DY, Kim MS, Han DJ, Kenmochi T, Mor E, Tisone G, Bernhardt P, Hernandez Gutierrez MP, Watarai Y. Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study. Expert Opin Drug Saf. 2020 Oct;19(10):1339-1348. doi: 10.1080/14740338.2020.1792441. Epub 2020 Jul 20.
PMID: 32633157DERIVEDBerger SP, Sommerer C, Witzke O, Tedesco H, Chadban S, Mulgaonkar S, Qazi Y, de Fijter JW, Oppenheimer F, Cruzado JM, Watarai Y, Massari P, Legendre C, Citterio F, Henry M, Srinivas TR, Vincenti F, Gutierrez MPH, Marti AM, Bernhardt P, Pascual J; TRANSFORM investigators. Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study. Am J Transplant. 2019 Nov;19(11):3018-3034. doi: 10.1111/ajt.15480. Epub 2019 Jul 1.
PMID: 31152476DERIVEDPascual J, Berger SP, Witzke O, Tedesco H, Mulgaonkar S, Qazi Y, Chadban S, Oppenheimer F, Sommerer C, Oberbauer R, Watarai Y, Legendre C, Citterio F, Henry M, Srinivas TR, Luo WL, Marti A, Bernhardt P, Vincenti F; TRANSFORM Investigators. Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation. J Am Soc Nephrol. 2018 Jul;29(7):1979-1991. doi: 10.1681/ASN.2018010009. Epub 2018 May 11.
PMID: 29752413DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharma
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
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
August 20, 2013
First Posted
September 26, 2013
Study Start
December 3, 2013
Primary Completion
February 1, 2017
Study Completion
January 17, 2018
Last Updated
January 30, 2019
Results First Posted
January 30, 2019
Record last verified: 2019-01