Concentration Controlled Everolimus With Reduced Dose Cyclosporine Versus Mycophenolate Mofetil With Standard Dose Cyclosporine in de Novo Renal Transplant Adult Recipients Treated With Basiliximab and Corticosteroids

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00658320
First received: April 10, 2008
Last updated: May 13, 2013
Last verified: May 2013
Results First Received: August 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Kidney Transplantation
Interventions: Drug: Everolimus
Drug: Mycophenolate mofetil (MMF)
Drug: Basiliximab
Drug: Cyclosporine A
Drug: Corticosteroid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Core Study randomization was conducted within 24 hours post reperfusion. Participants who completed the 12 month visit of the Core Study and met inclusion/exclusion criteria were eligible to participate in the Extension Study and continued the same treatment as the Core Study until Month 24.

Reporting Groups
  Description
Everolimus + Reduced Dose of Cyclosporine An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8 ng/mL). Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. Everolimus was available after 24 months for compassionate use.
Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study.

Participant Flow for 3 periods

Period 1:   Core Study: 12 Months
    Everolimus + Reduced Dose of Cyclosporine     Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine  
STARTED     61     61  
COMPLETED     56     58  
NOT COMPLETED     5     3  
Subject withdrew consent                 5                 3  

Period 2:   Extension Study: Month 12 to Month 24
    Everolimus + Reduced Dose of Cyclosporine     Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine  
STARTED     53     57  
Extension ITT: Received Study Drug     50     50  
COMPLETED     47     50  
NOT COMPLETED     6     7  
Subject withdrew consent                 3                 0  
Did not receive study drug in Extension                 3                 7  

Period 3:   Extension Study: After Month 24
    Everolimus + Reduced Dose of Cyclosporine     Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine  
STARTED     44     0  
COMPLETED     42     0  
NOT COMPLETED     2     0  
Subject withdrew consent                 2                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline Measures are based on the data obtained in the Core Study.

Reporting Groups
  Description
Everolimus + Reduced Dose of Cyclosporine An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Total Total of all reporting groups

Baseline Measures
    Everolimus + Reduced Dose of Cyclosporine     Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine     Total  
Number of Participants  
[units: participants]
  61     61     122  
Age  
[units: years]
Mean ± Standard Deviation
  42.5  ± 14.13     38.6  ± 11.36     40.5  ± 12.92  
Gender  
[units: participants]
     
Female     15     24     39  
Male     46     37     83  



  Outcome Measures
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1.  Primary:   Core Study: Number of Patients With Composite Efficacy Endpoint   [ Time Frame: 12 months ]

2.  Primary:   Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula   [ Time Frame: Month 24 ]

3.  Primary:   Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula   [ Time Frame: Month 48 ]

4.  Secondary:   Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up   [ Time Frame: 12 months ]

5.  Secondary:   Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula   [ Time Frame: Month 12 ]

6.  Secondary:   Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR)   [ Time Frame: 24 Months ]

7.  Secondary:   Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula   [ Time Frame: Month 24, Month 48 ]

8.  Secondary:   Extension Study: Number of Participants With Adverse Events and Serious Adverse Events   [ Time Frame: 24 Months ]

9.  Secondary:   Extension Study: Everolimus Trough Levels   [ Time Frame: Month 24, Month 48 ]

10.  Secondary:   Extension Study: Cyclosporine Trough Levels   [ Time Frame: Month 24, Month 48 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided


Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00658320     History of Changes
Obsolete Identifiers: NCT00856466
Other Study ID Numbers: CRAD001A1202
Study First Received: April 10, 2008
Results First Received: August 10, 2011
Last Updated: May 13, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare