Efficacy and Safety of Early Versus Delayed Administration of Everolimus in de Novo Renal Transplant Patients

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00154297
First received: September 8, 2005
Last updated: March 30, 2011
Last verified: March 2011
Results First Received: January 4, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Renal Transplantation
Intervention: Drug: Everolimus (RAD001)

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Immediate Everolimus Patients received Everolimus starting within 48 hours of kidney transplant through to the end of the study, administered orally twice a day. Dose was adjusted in order to maintain a trough level between 3-8 ng/mL.
Delayed Everolimus Patients received Everolimus 4 weeks after kidney transplant until the end of the study, administered orally twice a day. The dose was adjusted in order to maintain a trough level between 3-8 ng/mL. Patients received mycophenolic acid until everolimus was initiated.

Participant Flow:   Overall Study
    Immediate Everolimus     Delayed Everolimus  
STARTED     65 [1]   74 [1]
COMPLETED     57 [2]   67 [2]
NOT COMPLETED     8     7  
Death                 5                 2  
Withdrawal by Subject                 0                 5  
Lost to Follow-up                 3                 0  
[1] Randomized population.
[2] Completed study by 12 month.



  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.
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Reporting Groups
  Description
Immediate Everolimus Patients received Everolimus starting within 48 hours of kidney transplant through to the end of the study, administered orally twice a day. Dose was adjusted in order to maintain a trough level between 3-8 ng/mL.
Delayed Everolimus Patients received Everolimus 4 weeks after kidney transplant until the end of the study, administered orally twice a day. The dose was adjusted in order to maintain a trough level between 3-8 ng/mL. Patients received mycophenolic acid until everolimus was initiated.
Total Total of all reporting groups

Baseline Measures
    Immediate Everolimus     Delayed Everolimus     Total  
Number of Participants  
[units: participants]
  65     74     139  
Age [1]
[units: years]
Mean ± Standard Deviation
  57.3  ± 10.46     58.4  ± 9.86     57.9  ± 10.13  
Gender [1]
[units: participants]
     
Female     19     20     39  
Male     46     54     100  
[1] baseline measure based on randomized population.



  Outcome Measures
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1.  Primary:   Number of Participants Considered in Failure for the Primary Failure Endpoint at 3 Months   [ Time Frame: Month 3 ]

2.  Secondary:   Number of Participants Considered in Failure for the Primary Failure Endpoint at 6 Months Post-transplantation.   [ Time Frame: at 6 Month post-transplantation ]

3.  Secondary:   Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation.   [ Time Frame: at 12 Month post-transplantation ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation.
Measure Description

The primary efficacy variable was the “primary failure endpoint” at 12 months defined as the occurrence of one or more of the following events within the first 12 months:

  • delayed graft function (DGF), defined as the need for dialysis within the first 7 days post-transplantation excluding the first day post-transplantation
  • efficacy failure (biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up)
  • wound healing disorder related to initial transplant surgery
Time Frame at 12 Month post-transplantation  
Safety Issue No  

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.
Intention to treat (ITT) population.

Reporting Groups
  Description
Immediate Everolimus Patients received Everolimus starting within 48 hours of kidney transplant through to the end of the study, administered orally twice a day. Dose was adjusted in order to maintain a trough level between 3-8 ng/mL.
Delayed Everolimus Patients received Everolimus 4 weeks after kidney transplant until the end of the study, administered orally twice a day. The dose was adjusted in order to maintain a trough level between 3-8 ng/mL. Patients received mycophenolic acid until everolimus was initiated.

Measured Values
    Immediate Everolimus     Delayed Everolimus  
Number of Participants Analyzed  
[units: participants]
  65     74  
Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation.  
[units: Participants]
   
Failure at month 12 - Total     42     49  
Dialysis within first 7 days     16     18  
Efficacy failure (Total)     22     25  
--BPAR     13     15  
--Graft Loss     6     5  
--Death     5     2  
--Lost to follow-up (composite efficacy endpoint)     0     5  
Wound healing disorder     26     28  
Loss to follow-up for the primary failure endpoint     0     3  

No statistical analysis provided for Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation.



4.  Secondary:   Number of Participants Who Underwent Any Dialysis Within the 12-month Treatment Period   [ Time Frame: Month 12 ]

5.  Secondary:   Duration of Dialysis   [ Time Frame: 12 months ]

6.  Secondary:   Number of Participants With Any Wound Healing Disorder During the 12-month Treatment Period   [ Time Frame: Month 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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