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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01150097




Registration number
NCT01150097
Ethics application status
Date submitted
23/04/2010
Date registered
24/06/2010
Date last updated
7/11/2018

Titles & IDs
Public title
Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients
Scientific title
Extension Study to the Multicenter, Open-label, Randomized, Controlled Study CRAD001H2304 to Evaluate the Long-term Efficacy and Safety of Concentration-controlled Everolimus in Liver Transplant Recipient
Secondary ID [1] 0 0
2009-017311-15
Secondary ID [2] 0 0
CRAD001H2304E1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Transplant Recipient 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tacrolimus (reduced tacrolimus)
Treatment: Drugs - Everolimus (reduced tacrolimus)
Treatment: Drugs - Tacrolimus (tacrolimus elimination)
Treatment: Drugs - Everolimus (tacrolimus elimination)
Treatment: Drugs - Tacrolimus (tacrolimus control)
Treatment: Drugs - Corticosteroids

Experimental: Everolimus + reduced tacrolimus - Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.

Experimental: Tacrolimus elimination - Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.

Active comparator: Tacrolimus control - Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.


Treatment: Drugs: Tacrolimus (reduced tacrolimus)
After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.

Treatment: Drugs: Everolimus (reduced tacrolimus)
Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study.

Treatment: Drugs: Tacrolimus (tacrolimus elimination)
After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4.

Treatment: Drugs: Everolimus (tacrolimus elimination)
Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL.

Treatment: Drugs: Tacrolimus (tacrolimus control)
Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study.

Treatment: Drugs: Corticosteroids
For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6. The corticosteroids were not specified in the protocol because they were adminsitered to the participants according to local practice as part of standard of care.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
Timepoint [1] 0 0
from months 24 to 36
Primary outcome [2] 0 0
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
Timepoint [2] 0 0
from months 36 to 48
Primary outcome [3] 0 0
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
Timepoint [3] 0 0
from months 24 to 36
Primary outcome [4] 0 0
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
Timepoint [4] 0 0
from months 36 - 48
Primary outcome [5] 0 0
Change in Renal Function
Timepoint [5] 0 0
from months 24 to 36
Secondary outcome [1] 0 0
Incidence Rate of tBPAR
Timepoint [1] 0 0
from months 24 - 36

Eligibility
Key inclusion criteria
* Written informed consent
* Ability and willingness to adhere to study regimen
* Completed core study with assigned regimen;
Minimum age
20 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

* Severe hypercholesterolemia or hypertriglyceridemia.
* Low platelet count.
* Low white blood cell count.
* Positive test for human immunodeficiency virus (HIV).
* Systemic infection requiring active use of IV antibiotics.
* Patients in a critical care setting.
* Use of prohibited medication.
* Use of immunosuppressive agents not utilized in the protocol.
* Hypersensitivity to any of the study drugs or similar drugs.
* Pregnant or nursing (lactating) women
* Women of child-bearing potential not using a highly effective method of birth control.

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/03/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/05/2013
Sample size
Target
Accrual to date
Final
284
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [3] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5041 - Bedford Park
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
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United States of America
State/province [2] 0 0
Florida
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United States of America
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Kentucky
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United States of America
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Michigan
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Minnesota
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Missouri
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New Jersey
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New York
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United States of America
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North Carolina
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United States of America
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Oklahoma
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United States of America
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South Carolina
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United States of America
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Texas
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Argentina
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Buenos Aires
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Brazil
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RJ
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Brazil
State/province [18] 0 0
RS
Country [19] 0 0
Colombia
State/province [19] 0 0
Valle Del Cauca
Country [20] 0 0
Colombia
State/province [20] 0 0
Bogota
Country [21] 0 0
Czechia
State/province [21] 0 0
Czech Republic
Country [22] 0 0
France
State/province [22] 0 0
Bordeaux Cedex
Country [23] 0 0
France
State/province [23] 0 0
Clichy
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France
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Creteil
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France
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Marseille
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France
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Montpellier
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France
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Villejuif
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Germany
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Bavaria
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Germany
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Berlin
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Germany
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Essen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
State/province [33] 0 0
Leipzig
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Germany
State/province [34] 0 0
Mainz
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Ireland
State/province [35] 0 0
Dublin 4
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Italy
State/province [36] 0 0
MI
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Italy
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MO
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Italy
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PI
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Italy
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RM
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Italy
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TO
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Netherlands
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Rotterdam
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Russian Federation
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Moscow
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Spain
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Barcelona
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Vizcaya
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Sweden
State/province [47] 0 0
Stockholm
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The reason for this extension is to evaluate the long-term safety and efficacy of two concentration-controlled everolimus regimen in de novo liver transplant recipients. The most important long-term safety assessments include evaluation of renal function, progression of HCV related allograft fibrosis, and other treatment related effects at Month 36 post-transplantation compared to extension baseline (Months 24 post-transplantation).
Trial website
https://clinicaltrials.gov/study/NCT01150097
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01150097