De Novo Everolimus Versus Tacrolimus in Combination With Mofetil Mycophenolate and Low Dose Corticosteroids to Reduce Tacrolimus Induced Nephrotoxicity in Liver Transplantation: a Prospective, Multicentric, Randomised Study

NCT ID: NCT02909335

Last Updated: 2022-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Study Completion Date

2021-11-30

Brief Summary

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Tacrolimus is a calcineurin inhibitor. This is the immunosuppression of reference for patients undergoing a first liver transplant. This treatment can prevent graft rejection, but can cause side effects including kidney failure (in 25% after the first year).

Everolimus is an immunosuppressive that effectively prevents acute rejection in heart and kidney transplant recipients. It preserves renal function when it is started soon after the transplant, i.e. before a severe dysfunction is installed.

Detailed Description

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In the liver transplant, early interruption of calcineurin inhibitors with a quick relay everolimus monotherapy preserves renal function and is associated with a lower acute rejection rate.

We wish to assess whether the introduction of a de novo immunosuppression everolimus under protection of basiliximab induction, mycophenolate mofetil and then low doses of corticosteroids, reduces the nephrotoxicity of immunosuppressive therapy in liver transplant patients, compared to a standard protocol with tacrolimus associated with mycophenolate mofetil and low dose corticosteroids.

Conditions

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Liver Transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Tacrolimus group

Tacrolimus + mycophenolate mofetil + corticosteroids

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

Everolimus is administered at an initial dose of 1.5 mg twice a day on Day 5.

The doses are then adjusted to maintain trough levels:

* between 6 and 10 ng / ml during the first 2 months,
* between 5-8 ng / ml from the start of the end M3 and M6,
* and between 4 and 6 ng / ml between the beginning and the end of M7 M12.

Mycophenolate mofetil

Intervention Type DRUG

mycophenolate mofetil is administered similarly in the two groups at the dose of 1.5 g for the first two months and then 1 g twice a day. The doses may be adjusted according to the tolerance of the product.

Prednisolone, Prednisone or Methylprednisolone

Intervention Type DRUG

Corticosteroid is similarly administered in both groups between baseline and the end of M6 and adjusted in case of acute rejection

Everolimus group

Everolimus + mycophenolate mofetil + corticosteroids

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type DRUG

Tacrolimus is administered at an initial dose of 0.040 mg / kg twice a day on Day 5.

The doses are then adjusted to maintain trough levels :

* between 6 and 10 ng / ml during the first 2 months,
* between 5 and 8 ng / ml from the start of the end M3 and M6,
* and between 4 and 6 ng / ml between the beginning and the end of M7 M12.

Mycophenolate mofetil

Intervention Type DRUG

mycophenolate mofetil is administered similarly in the two groups at the dose of 1.5 g for the first two months and then 1 g twice a day. The doses may be adjusted according to the tolerance of the product.

Prednisolone, Prednisone or Methylprednisolone

Intervention Type DRUG

Corticosteroid is similarly administered in both groups between baseline and the end of M6 and adjusted in case of acute rejection

Interventions

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Tacrolimus

Tacrolimus is administered at an initial dose of 0.040 mg / kg twice a day on Day 5.

The doses are then adjusted to maintain trough levels :

* between 6 and 10 ng / ml during the first 2 months,
* between 5 and 8 ng / ml from the start of the end M3 and M6,
* and between 4 and 6 ng / ml between the beginning and the end of M7 M12.

Intervention Type DRUG

Everolimus

Everolimus is administered at an initial dose of 1.5 mg twice a day on Day 5.

The doses are then adjusted to maintain trough levels:

* between 6 and 10 ng / ml during the first 2 months,
* between 5-8 ng / ml from the start of the end M3 and M6,
* and between 4 and 6 ng / ml between the beginning and the end of M7 M12.

Intervention Type DRUG

Mycophenolate mofetil

mycophenolate mofetil is administered similarly in the two groups at the dose of 1.5 g for the first two months and then 1 g twice a day. The doses may be adjusted according to the tolerance of the product.

Intervention Type DRUG

Prednisolone, Prednisone or Methylprednisolone

Corticosteroid is similarly administered in both groups between baseline and the end of M6 and adjusted in case of acute rejection

Intervention Type DRUG

Other Intervention Names

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Prograf Certican Cellcept Methylprednisolone: Solumedrol® Prednisolone: Solupred® Prednisone: Cortancyl®

Eligibility Criteria

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Inclusion Criteria

* Adults (≥18 years), male or female,
* Patients due to receive a first liver transplant with a full or reduced graft taken from a donor brain-dead beating heart or a related living donor,
* Patients having given a free and informed written consent .


* Receiving basiliximab (Simulect)
* Whose immunosuppression regimen from day 5 could immediately consist of either tacrolimus or everolimus, in combination with mycophenolate mofetil and low dose corticosteroids
* With hepatic artery permeable to echo Doppler 4 days after transplant.

Exclusion Criteria

* History of immunosuppressive therapy,
* Known hypersensitivity to the treatments or macrolides,
* HIV infection
* Autoimmune hepatitis,
* Primary sclerosing cholangitis,
* Programming or realization of a combined transplant,
* Pregnancy or lack of effective contraception,
* Breastfeeding.
* Incompatibility with the donor,
* Thrombosis of the hepatic artery between D0 and D4,
* Non-primary graft function leading to a re-registration on the waiting list.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karim BOUDJEMA, MD, PhD

Role: STUDY_DIRECTOR

CHU Rennes

Countries

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France

Other Identifiers

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2013-003802-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

35RC12_8985

Identifier Type: -

Identifier Source: org_study_id