Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01025817
First received: November 19, 2009
Last updated: June 5, 2014
Last verified: April 2014

November 19, 2009
June 5, 2014
January 2010
March 2013   (final data collection date for primary outcome measure)
Number of Participants With Incidence of Composite Efficacy Failure [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)*, (2) graft loss**, (3) participant death or(4) loss to follow-up. *A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. **Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.
Composite efficacy failure rates demonstrated by treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01025817 on ClinicalTrials.gov Archive Site
  • Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR [mL/min/1.73m˄2] = 186.3*(C˄-1.154)*(A˄-0.203)*G*R. DEFINITIONS: C = serum concentration of creatinine [mg/dL]; A = age [years]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
  • Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.
  • Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.
  • Number of Participants With Incidence of New Onset of Diabetes Mellitus [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant, or with a random plasma glucose ≥200 mg dL (11.1 mmol/L) with 2 fasting plasma glucose values ≥126 mg/dL (7 mmol/L)
  • Number of Participants With Incidence of Proteinuria Events [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Number of participants with Incidence of proteinuria events indicating chronic kidney disease
  • Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class
  • To compare renal function (GFR (glomerular filtration rate)) of everolimus with low dose tacrolimus regimen to that of CellCept® with standard dose tacrolimus regimen [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Incidence of CMV (viremia, syndrome and disease) and BKV (viremia, viruria, or nephropathy) [ Time Frame: Day 28 and Months 2, 3, 4, and 6 ] [ Designated as safety issue: No ]
  • Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant [ Time Frame: Days 1, 3, 5, 7, 14, and 28 and Months 2, 3, 4, 6, 7, 9, and 12 ] [ Designated as safety issue: No ]
  • Incidence of chronic kidney disease with associated proteinuria [ Time Frame: Days 1, 7, 14, and 28 and Months 2, 3, 4, 6, 7, 9, and 12 ] [ Designated as safety issue: No ]
  • Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events [ Time Frame: Days 1, 3, 4, 5, 7, 14, and 28 and Months 2, 3, 4, 6, 7, 9, and 12 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients
A 12 Month, Multi-center, Randomized, Open-label Non-inferiority Study Comparing Safety and Efficacy of Concentration-controlled Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in de Novo Renal Transplant Recipients

The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Kidney Transplant
  • Drug: Everolimus and tacrolimus

    Everolimus:

    • Dosage form: 0.75 mg, 0.25 mg, and 0.5 mg tablets
    • Dose: 1.5 mg per day
    • Frequency: 0.75 mg twice daily

    Tacrolimus:

    • Dose adjusted to maintain specific blood levels
  • Drug: mycophenolate mofetil and tacrolimus
    Mycophenolate mofetil: - Dose form: 250 mg capsule - Dose: 2g per day - Frequency: 1g twice daily Tacrolimus: - Dose adjusted to maintain specific blood levels
    Other Name: Active Comparator Control)
  • Experimental: Everolimus (EVR) & low dose of tacrolimus
    Everolimus (EVR) and tacrolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was < 3 ng/mL, or reduced if the trough level was > 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
    Intervention: Drug: Everolimus and tacrolimus
  • Active Comparator: Mycophenolate mofetil & standard dose tacrolimus
    Mycophenolate mofetil and tacrolimus (MMF) treatment arm: MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. Tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, target level of tacrolimus was reduced to 5 - 8 ng/mL.
    Intervention: Drug: mycophenolate mofetil and tacrolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
613
March 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Male or female renal recipients 18-70 years of age undergoing kidney transplantation, either primary or re-transplant;
  • Recipient of a cadaveric, deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death), living unrelated or non-HLA identical living related donor kidney;
  • Graft must be functional (producing greater than or equal to 100 ml of urine within 24 hours after transplantation) at time of randomization.

Exclusion criteria:

  • Donor organ with a cold ischemic time > 30 hours;
  • Males or females who produce less than 100 ml of urine in the first 24 hours post-transplantation;
  • Males or females who are recipients of ABO incompatible transplants, or T cell, or B cell crossmatch positive transplant;
  • Males or females with severe total hypercholesterolemia or total hypertriglyceridemia (Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable);
  • Males or females who have any surgical or any medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might alter the absorption, distribution, metabolism and/or excretion of study medication.

Other protocol related inclusion/exclusion criteria may apply.

Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01025817
CRAD001AUS92
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP