Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.

NCT ID: NCT01598987

Last Updated: 2017-05-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2016-06-30

Brief Summary

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This study was designed to assess the evolution of renal function and to collect efficacy, safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric liver transplant recipients.

Detailed Description

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Study is completed (was active and ongoing but no longer recruiting since December 2014). The study Data Monitoring Committee meeting communicated to Novartis the following safety findings in the study population: high rate of premature discontinuation of study medication, high rate of post-transplant lymphoproliferative disease and high rate of related serious infections leading to hospitalization. In light of the safety findings, Novartis followed the DMC recommendation to discontinue the study medication in this age group and to stop enrolling new patients in this study (regardless of age).

Conditions

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Renal Function Liver Transplant

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Everolimus based regimen

Conversion at Baseline from an immunosuppressive regimen which contains either cyclosporine (CsA) or tacrolimus (TAC) with or without mycophenolic acid (MPA), with or without corticosteroids in a regimen which contains everolimus combined reduced dose of either cyclosporine (CsA) or tacrolimus (TAC).

The dosing schedule was twice daily, 12 hours apart.

Group Type EXPERIMENTAL

Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.

Intervention Type DRUG

Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m\^2/dose in combination wit Cyclosporine A or 2.0 mg/m\^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml.

Interventions

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Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.

Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m\^2/dose in combination wit Cyclosporine A or 2.0 mg/m\^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Signed informed consent from both parents or legal guardian(s) prior to patient participation in the study.

Paediatric liver transplant recipients aged greater than or equal to 1 month and younger than 18 years of age.

Paediatric recipients at the earliest 1 month and latest 6 month after liver transplantation.

Exclusion Criteria

Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant hepatitis /acute liver failure.

Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins, portal vein or inferior vena cava at any time prior to the start of study drug.

Patients with serum creatinine value \>2 times age-related ULN at Baseline or who received renal replacement therapy within one week prior to the start of study drug and patients with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion \>500 mg/m2/24 hrs, at Baseline.

Patients with clinically significant systemic infection and/or in a critical care setting requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.

Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.

Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (\>9 mIU/mL) at Baseline.

Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they agree for abstinence from sexual activity.
Minimum Eligible Age

1 Month

Maximum Eligible Age

17 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

Los Angeles, California, United States

Site Status

Novartis Investigative Site

New Haven, Connecticut, United States

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Chicago, Illinois, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Charleston, South Carolina, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Madison, Wisconsin, United States

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Parkville, Victoria, Australia

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Brussels, , Belgium

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Edmonton, Alberta, Canada

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København Ø, , Denmark

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Bron, , France

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Hanover, Germany, Germany

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Bonn, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Regensburg, , Germany

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Tübingen, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Bergamo, BG, Italy

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Roma, ITA, Italy

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Padua, PD, Italy

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Torino, TO, Italy

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Barcelona, Catalonia, Spain

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Madrid, Madrid, Spain

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Stockholm, , Sweden

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West Midlands, Birmingham, United Kingdom

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Leeds, , United Kingdom

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Novartis Investigative Site

London, , United Kingdom

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Countries

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United States Australia Belgium Canada Denmark France Germany Hungary Italy Spain Sweden United Kingdom

Other Identifiers

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2011-003069-14

Identifier Type: -

Identifier Source: secondary_id

CRAD001H2305

Identifier Type: -

Identifier Source: org_study_id

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