Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)

NCT ID: NCT01950819

Last Updated: 2019-01-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

2037 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-03

Study Completion Date

2018-01-17

Brief Summary

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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.

Detailed Description

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Conditions

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End Stage Renal Disease (ESRD) Chronic Kidney Disease (CKD) Hemodialysis Renal Replacement Therapy Renal Transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Open-label study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

Induction therapy

Intervention Type BIOLOGICAL

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

Corticosteroids

Intervention Type DRUG

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.

EVR+rCNI

Intervention Type DRUG

Everolimus 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

Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

Group Type ACTIVE_COMPARATOR

Induction therapy

Intervention Type BIOLOGICAL

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

Corticosteroids

Intervention Type DRUG

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.

MPA+sCNI

Intervention Type DRUG

Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

Interventions

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Induction therapy

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

Intervention Type BIOLOGICAL

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.

Intervention Type DRUG

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)

Intervention Type DRUG

MPA+sCNI

Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

Intervention Type DRUG

Other Intervention Names

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Simulect, basiliximab, rATG, Thymoglobulin prednisone, methylprednisone, methylprednisolone, etc. Zortress, Certican, Neoral, Prograf Myfortic, Cellcept, Neoral, Prograf

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Birmingham, Alabama, United States

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Loma Linda, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Burlington, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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Livingston, New Jersey, United States

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Buffalo, New York, United States

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The Bronx, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Harrisburg, Pennsylvania, United States

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Providence, Rhode Island, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Milwaukee, Wisconsin, United States

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CABA, Buenos Aires, Argentina

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San Martín, Buenos Aires, Argentina

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Ljubljana, , Slovenia

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Granada, Andalusia, Spain

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L'Hospitalet de Llobregat, Barcelona, Spain

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Zaragoza, , Spain

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Gothenburg, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Bern, , Switzerland

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Tainan City, Taiwan ROC, Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Ratchathewi, Bangkok, Thailand

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Antalya, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Mecidiyekoy/Istanbul, , Turkey (Türkiye)

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Countries

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United States Argentina Australia Austria Belgium Brazil Bulgaria Chile Colombia Croatia Czechia Egypt France Germany Greece India Israel Italy Japan Kuwait Lebanon Malaysia Mexico Netherlands Norway Philippines Poland Portugal Russia Saudi Arabia Serbia Singapore Slovakia Slovenia South Africa South Korea Spain Sweden Switzerland Taiwan Thailand Turkey (Türkiye)

References

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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.

Reference Type DERIVED
PMID: 34620664 (View on PubMed)

Watarai 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.

Reference Type DERIVED
PMID: 34216395 (View on PubMed)

Citterio 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.

Reference Type DERIVED
PMID: 32633157 (View on PubMed)

Berger 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.

Reference Type DERIVED
PMID: 31152476 (View on PubMed)

Pascual 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.

Reference Type DERIVED
PMID: 29752413 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-000322-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001A2433

Identifier Type: -

Identifier Source: org_study_id

NCT02316938

Identifier Type: -

Identifier Source: nct_alias

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