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 (FOREVER)

Rennes University Hospital

Status and phase: Withdrawn; Phase 3

Conditions: Liver Transplantation

Treatments: Drug: Prednisolone, Prednisone or Methylprednisolone; Drug: Everolimus; Drug: Mycophenolate mofetil; Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT02909335

2013-003802-19 (EudraCT Number)

35RC12_8985

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Pre-transplantation 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 .

Post-transplantation Inclusion criteria: Patients meeting the following criteria will be included:

• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Tacrolimus group

Active Comparator group

Description:

Tacrolimus + mycophenolate mofetil + corticosteroids

Treatment:

Drug: Mycophenolate mofetil

Drug: Everolimus

Drug: Prednisolone, Prednisone or Methylprednisolone

Everolimus group

Experimental group

Description:

Everolimus + mycophenolate mofetil + corticosteroids

Treatment:

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Drug: Prednisolone, Prednisone or Methylprednisolone