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Completed

NCT Number: NCT01950819

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

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.

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Key information

Conditions

End Stage Renal Disease (ESRD) Chronic Disease Chronic Kidney Disease (CKD) Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hemodialysis Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Renal Replacement Therapy Renal Transplantation Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigative Site, CABA, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.
  • Subject with white blood cell (WBC) count ≤ 2,000 /mm3 or with platelet count ≤ 50,000 /mm3.
  • Pregnant or nursing (lactating) women.
  • 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.

Treatment and study plan

Induction therapy

Biological

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

Other names: Simulect, basiliximab, rATG, Thymoglobulin

Corticosteroids

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.

Other names: prednisone, methylprednisone, methylprednisolone, etc.

EVR+rCNI

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)

Other names: Zortress, Certican, Neoral, Prograf

MPA+sCNI

Drug

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

Other names: Myfortic, Cellcept, Neoral, Prograf

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.

    Time frame: Month 12 is Primary, Month 24 secondary

    Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2.

Secondary outcomes

  1. Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death

    Time frame: Month 12 and 24

    Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death

  2. Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2

    Time frame: Month 12 and 24

    Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR < 50 mL/min/1.73m2

  3. Incidence of Failure on the Composite Endpoint of Graft Loss or Death.

    Time frame: Month 12 and 24

    Incidence of failure on the composite endpoint of graft loss or death.

  4. Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection

    Time frame: Month 12 and 24

    Incidence of death, graft loss, tBPAR (treated biopsy proven acute rejection), BPAR (biopsy proven acute rejection), tAR (treated acute rejection), AR (acute rejection) and humoral rejection (aAMR : active antibody mediated rejection and cAMR: chronic antibody mediated rejection)

  5. Incidence of eGFR < 50 mL/Min/1.73m2

    Time frame: Month 12 and 24

    Incidence of eGFR < 50 mL/min/1.73m2

  6. Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR

    Time frame: Baseline (week 4), Month 12 and 24

    Renal allograft function : mean estimated glomerular filtration rate, eGFR

  7. Evolution of Renal Function, as eGFR, Over Time by Slope Analysis.

    Time frame: Month 12 and 24

    Rate of change of renal function, as eGFR, calculated using MDRD4 formula (Coresh, 2003) and adjusted by covariates.

  8. Renal Function Assessed by Creatinine Lab Values

    Time frame: Month 12 and 24

    Mean Renal function as assessed in clinical practice, by ceatinine values. Analysis is done without considering missing values for analysis.

  9. Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported

    Time frame: Month 12 and 24

    Mean Renal function as used in clinical practice, using different formula for calculation of renal function than MDRD4 (our primary efficacy parameter), and other alternate formulae (e.g. CKD-EPI). Analysis is done without considering missing values for analysis.

  10. Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation.

    Time frame: Month 24

    Incidence of adverse events, serious adverse events and adverse events leading to study regimen discontinuation.

  11. Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events.

    Time frame: Month 24

    Incidence of cytomegalovirus and BK virus, new onset diabetes mellitus, chronic kidney disease with associated proteinuria and calcineurin inhibitor associated adverse events.

  12. Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios.

    Time frame: Baseline, Month 12 and 24

    Mean urinary protein and albumin excretion by treatment estimated by mean urinary protein/creatinine and urinary albumin/creatinine ratios.

  13. Incidence of Major Cardiovascular Events.

    Time frame: Month 24

    Incidence of major cardiovascular events by Preferred Term

  14. Incidence of Malignancies.

    Time frame: Month 24

    Incidence of malignancies.

  15. 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.

    Time frame: Month 12 and 24

    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.

  16. Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants)

    Time frame: Month 12 and 24

    Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity:

    • Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IIA - Mild to moderate intimal arteritis
    • Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
    • Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

  17. Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events)

    Time frame: Month 12 and 24

    Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity:

    • Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IIA - Mild to moderate intimal arteritis
    • Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
    • Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

  18. Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections

    Time frame: Month 12 and 24

    Incidence of tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), excluding grade IA rejections. Grades for T-cell mediated rejection, with increasing severity:

    • Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
    • Type IIA - Mild to moderate intimal arteritis
    • Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
    • Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

  19. Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup

    Time frame: Month 12 and 24

    Incidence of composite of tBPAR or eGRF<50 mL/min/1.73m2 by subgroup

  20. Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2

    Time frame: Month 12 and 24

    Incidence of tBPAR (excluding grade IA rejections) or GFR<50 mL/min/1.73m2

  21. Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up

    Time frame: Month 12 and 24

    Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death or loss to follow-up

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: TRANSFORM

Important dates

Study start
2013
Primary completion
2017
Study completion
2018
First posted
Sep 26, 2013
Registry last updated
Jan 30, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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