A National Multi-center Randomized, Open Label Study to Evaluate Efficacy and Safety of Everolimus With EC-MPS Compared to Standard Treatment Combination Tacrolimus and EC-MPS in de Novo Liver Transplant Recipients (SIMCER)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01625377
First received: June 19, 2012
Last updated: March 25, 2016
Last verified: March 2016
Results First Received: March 25, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Liver Transplantation
Interventions: Drug: tacrolimus
Drug: everolimus
Drug: Basiliximab
Drug: Mycophenolic Acid
Drug: Corticosteroids

  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
Total 188 patients were randomized

Reporting Groups
  Description
Tacrolimus From transplantation to randomization: Basiliximab (20mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Everolimus (RAD001)

From transplantation to randomization: Basiliximab (20mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.

From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).


Participant Flow:   Overall Study
    Tacrolimus     Everolimus (RAD001)  
STARTED     95 [1]   93  
Safety Set of Population     94     90  
Intent to Treat Population     93     90  
COMPLETED     88     71  
NOT COMPLETED     7     22  
Death                 1                 1  
Administrative Problem                 1                 1  
Protocol Violation                 0                 3  
Adverse Event                 3                 16  
Graft loss                 1                 0  
Unsatisfactory therapeutic effect                 0                 1  
Abnormal laboratory values                 1                 0  
[1] "Started" indicates randomized patients.



  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.
Randomized population

Reporting Groups
  Description
Tacrolimus From transplantation to randomization: Basiliximab (20mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Everolimus (RAD001)

From transplantation to randomization: Basiliximab (20mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.

From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).

Total Total of all reporting groups

Baseline Measures
    Tacrolimus     Everolimus (RAD001)     Total  
Number of Participants  
[units: participants]
  95     93     188  
Age  
[units: Years]
Mean (Standard Deviation)
  55.5  (8.24)     56.5  (8.59)     56.0  (8.41)  
Gender  
[units: Participants]
     
Female     14     14     28  
Male     81     79     160  



  Outcome Measures
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1.  Primary:   Change From Baseline (Randomization) in Renal Function   [ Time Frame: Baseline, Week 24 ]

2.  Secondary:   Number of Patients With Treatment Failures   [ Time Frame: At week 12 and week 24 ]

3.  Secondary:   Number of Patients With Treated or Not Treated Biopsy Proven Acute Rejection (BPAR)   [ Time Frame: at 12 week and 24 week ]

4.  Secondary:   Number of Patients Reported With Different Categories of Severity of BPAR According to Banff Classification   [ Time Frame: at 12 week and 24 week ]

5.  Secondary:   Number of Patients With Treated or Untreated BPAR With RAI Score Greater Than 3   [ Time Frame: At 24 weeks ]

6.  Secondary:   Number of Patients With Death or Graft Loss   [ Time Frame: at week 24 ]

7.  Secondary:   Change From Baseline (Randomization) in Serum Creatinine   [ Time Frame: Baseline, Week 24 ]

8.  Secondary:   Change From Baseline (Randomization) in Urine Protein/Creatinine Ratio   [ Time Frame: Baseline, week 24 ]

9.  Secondary:   Change From Baseline (Randomization) in Creatinine Clearance Estimated Using the Adjusted Cockcroft-Gault Formula   [ Time Frame: Baseline, Week 24 ]

10.  Secondary:   Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by Abbreviated Modification of Diet in Renal Disease (MDRD) Formula   [ Time Frame: Baseline, Week 24 ]

11.  Secondary:   Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by CKD-EPI Formula   [ Time Frame: Baseline, Week 24 ]

12.  Secondary:   Number of Patients in Different Stages of Chronic Kidney Diseases According to the K/DOQI Classification System   [ Time Frame: At Week 24 ]

13.  Secondary:   Number of Patients With Any Adverse Events, Serious Adverse Events, Death and Premature Discontinuation   [ Time Frame: Baseline to 24 weeks ]


  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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  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.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01625377     History of Changes
Other Study ID Numbers: CRAD001HFR02
2012-000137-39 ( EudraCT Number )
Study First Received: June 19, 2012
Results First Received: March 25, 2016
Last Updated: March 25, 2016
Health Authority: France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)