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 (SIMCER)

Novartis

Status and phase: Completed; Phase 3

Conditions: Liver Transplantation

Treatments: Drug: tacrolimus; Drug: Corticosteroids; Drug: everolimus; Drug: Basiliximab; Drug: Mycophenolic Acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01625377

CRAD001HFR02

2012-000137-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 188 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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188 participants in 2 patient groups

Tacrolimus

Active Comparator group

Description:

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

Treatment:

Drug: Mycophenolic Acid

Drug: Basiliximab

Drug: Corticosteroids

Drug: tacrolimus

Everolimus (RAD001)

Experimental group

Description:

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).

Treatment:

Drug: Mycophenolic Acid

Drug: Basiliximab

Drug: Corticosteroids

Drug: everolimus

Drug: tacrolimus