Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients

NCT ID: NCT01150097

Last Updated: 2018-11-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

284 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2013-05-03

Brief Summary

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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).

Detailed Description

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Conditions

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Liver Transplant Recipient

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Everolimus + reduced tacrolimus

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

Group Type EXPERIMENTAL

Tacrolimus (reduced tacrolimus)

Intervention Type DRUG

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.

Everolimus (reduced tacrolimus)

Intervention Type DRUG

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.

Corticosteroids

Intervention Type DRUG

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.

Tacrolimus elimination

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

Group Type EXPERIMENTAL

Tacrolimus (tacrolimus elimination)

Intervention Type DRUG

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.

Everolimus (tacrolimus elimination)

Intervention Type DRUG

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.

Corticosteroids

Intervention Type DRUG

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.

Tacrolimus control

Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.

Group Type ACTIVE_COMPARATOR

Tacrolimus (tacrolimus control)

Intervention Type DRUG

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.

Corticosteroids

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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FK-506, fujimycin, Prograf, Advagraf, Protopic RAD001, Zortress, Certican, Afinitor FK-506, fujimycin, Prograf, Advagraf, Protopic RAD001, Zortress, Certican, Afinitor FK-506, fujimycin, Prograf, Advagraf, Protopic

Eligibility Criteria

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Inclusion Criteria

* Written informed consent
* Ability and willingness to adhere to study regimen
* Completed core study with assigned regimen;

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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Washington D.C., District of Columbia, United States

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Tampa, Florida, United States

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Lexington, Kentucky, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Newark, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Charleston, South Carolina, United States

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Houston, Texas, United States

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Houston, Texas, United States

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CABA, Buenos Aires, Argentina

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San Martín, Buenos Aires, Argentina

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Camperdown, New South Wales, Australia

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Bedford Park, South Australia, Australia

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Heidelberg, Victoria, Australia

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Rio de Janeiro, Rio de Janeiro, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Cali, Valle del Cauca Department, Colombia

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Bogotá, , Colombia

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Prague, Czech Republic, Czechia

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Bordeaux, , France

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Clichy, , France

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Créteil, , France

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Marseille, , France

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Montpellier, , France

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Villejuif, , France

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Regensburg, Bavaria, Germany

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Berlin, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Dublin, , Ireland

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Milan, MI, Italy

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Modena, MO, Italy

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Pisa, PI, Italy

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Roma, RM, Italy

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Torino, TO, Italy

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Rotterdam, , Netherlands

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Moscow, , Russia

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Moscow, , Russia

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L'Hospitalet de Llobregat, Barcelona, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Valencia, Valencia, Spain

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Barakaldo, Vizcaya, Spain

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Stockholm, , Sweden

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Edinburgh, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Colombia Czechia France Germany Ireland Italy Netherlands Russia Spain Sweden United Kingdom

Other Identifiers

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2009-017311-15

Identifier Type: -

Identifier Source: secondary_id

CRAD001H2304E1

Identifier Type: -

Identifier Source: org_study_id

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