Table 3 Objectives of the Hephaistos study

Primary objective

To demonstrate that an immunosuppressive regimen based on everolimus with reduced tacrolimus has superior efficacy compared with tacrolimus alone on eGFR (MDRD-4 formula) at Month 12 in de novo liver transplant recipients

Key secondary objective

To evaluate the incidence of a composite of tBPAR, graft loss, or death at Month 12

Other key secondary efficacy objectives

• Incidence of individual and composite efficacy components (tBPAR, graft loss, death, or loss to follow-up) at Months 6 and 12

• To evaluate treated BPAR by: (1) incidence, (2) time to event, (3) severity, and (4) diagnosis leading to transplantation

• To evaluate any acute rejection by: (1) incidence, (2) time to event, and (3) severity

Other key renal function-related objectives

• Evolution of renal function (eGFR; MDRD-4) over time

• Renal function (eGFR by MDRD-4, Nankivell, Cockcroft-Gault, CKD-EPI, and Hoek formulae)

• To evaluate serum creatinine at various time points

• To evaluate renal function and change in eGFR from screening, randomization, and Week 2 post-transplantation to Months 6 and 12 in various subgroups

• To evaluate urinary protein/creatinine ratio and incidence of proteinuria at various time points

Other key safety-related objectives

• Incidence of adverse events/infections/serious adverse events

• Incidence of treatment-related side effects, such as NODM, evolution of metabolic parameters as subdivisions of serum/plasma lipid panel, neurotoxicity, and hypertension

• Incidence and reason for premature discontinuation of study medication and premature discontinuation from the study

Key virus (HCV and CMV)- and HCC-related objectives

• Incidence and rate of progression of HCV, HCV-related fibrosis, and HCV viral load

• Incidence of and response to HCV antiviral treatment

• Incidence of de novo HCC malignancies and rate of recurrence at Month 12

• Incidence and severity of CMV viral infections