Clinical trial NCT02909335: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Liver Transplantation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2016-09-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Worsening of renal function
timeFrame: Between the initiation of treatment (Day 5) and the end (week 48) (censored criterion)
measure: Occurrence of graft loss
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion
Secondary outcomes:
measure: Plasma creatinine
timeFrame: At the end of the treatment (week 48)
measure: Glomerular filtration rate
timeFrame: At the end of the treatment (week 48)
measure: Occurrence of mental trouble
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Occurence of convulsions
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Hypertension control
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Number of patients with incident diabetes
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Hypercholesterolemia
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Hypertriglyceridemia
timeFrame: Between the baseline and the end of the treatment (week 48) (censored criterion)
measure: Number of patients with infection
timeFrame: At the end of the treatment (week 48)
measure: Number of everolimus linked adverse events
timeFrame: At the end of the treatment (week 48)
measure: Number of mycophenolate mofetil linked adverse events
timeFrame: At the end of the treatment (week 48)
Other outcomes:
Locations:
Study officials:
affiliation: CHU Rennes
name: Karim BOUDJEMA, MD, PhD
role: STUDY_DIRECTOR
References: