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

NCT ID: NCT01625377

Last Updated: 2016-04-27

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

188 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2015-03-31

Brief Summary

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The aims of the study was to evaluate the safety and efficacy of early introduction one month post-transplantation of everolimus associated to EC-MPS with tacrolimus discontinuation in de novo liver transplant recipients and to evaluate if it leads to a better renal function 6 month post-transplantation compared to standard treatment associating tacrolimus and EC-MPS.

The renal function was estimated by glomerular filtration rate.

Detailed Description

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Conditions

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Liver Transplantation

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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Tacrolimus

From transplantation to randomization: Basiliximab (40mg) 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

Group Type ACTIVE_COMPARATOR

tacrolimus

Intervention Type DRUG

Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.

Basiliximab

Intervention Type DRUG

Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI). 20 mg at D0 and D4

Mycophenolic Acid

Intervention Type DRUG

Dose of 1440 mg/day from transplantation to month 6 post- transplantation

Corticosteroids

Intervention Type DRUG

Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice

Everolimus (RAD001)

From transplantation to randomization: Basiliximab (40mg) 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).

Group Type EXPERIMENTAL

tacrolimus

Intervention Type DRUG

Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.

everolimus

Intervention Type DRUG

Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation

Basiliximab

Intervention Type DRUG

Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI). 20 mg at D0 and D4

Mycophenolic Acid

Intervention Type DRUG

Dose of 1440 mg/day from transplantation to month 6 post- transplantation

Corticosteroids

Intervention Type DRUG

Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice

Interventions

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tacrolimus

Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.

Intervention Type DRUG

everolimus

Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation

Intervention Type DRUG

Basiliximab

Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI). 20 mg at D0 and D4

Intervention Type DRUG

Mycophenolic Acid

Dose of 1440 mg/day from transplantation to month 6 post- transplantation

Intervention Type DRUG

Corticosteroids

Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice

Intervention Type DRUG

Other Intervention Names

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Prograf® Certican® / RAD001 Simulect® Myfortic®

Eligibility Criteria

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Inclusion Criteria

* Man or woman aged 18 years or greater, recipient of a primary liver transplant from a deceased donor with whole or split liver

Exclusion Criteria

* Patient recipient of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant
* Recipient of a liver from a living donor or cadaveric non heart beating donor
* ABO incompatible transplant graft
* Transplantation following autoimmune liver hepatitis, primitive sclerosing cholangitis or primitive biliary cirrhosis
* Estimated glomerular filtration rate ≤ 30ml/min at selection
* History of malignancy within the 5 past years, other than non-metastatic basal or squamous cell carcinoma and hepatocellular carcinoma
* Alpha-foeto-protein \> 1000 ng/ml (only in case of hepatocellular carcinoma)
Minimum Eligible Age

18 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

Besançon, , France

Site Status

Novartis Investigative Site

Bordeaux, , France

Site Status

Novartis Investigative Site

Chambray-lès-Tours, , France

Site Status

Novartis Investigative Site

Clichy, , France

Site Status

Novartis Investigative Site

Créteil, , France

Site Status

Novartis Investigative Site

Grenoble, , France

Site Status

Novartis Investigative Site

Lille, , France

Site Status

Novartis Investigative Site

Marseille, , France

Site Status

Novartis Investigative Site

Montpellier, , France

Site Status

Novartis Investigative Site

Nice, , France

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Rennes, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Countries

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France

Other Identifiers

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2012-000137-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001HFR02

Identifier Type: -

Identifier Source: org_study_id

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