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Table 3 Objectives of the Hephaistos study

From: Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial

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
  1. BPAR, biopsy-proven acute rejection; CKD-EPI, chronic kidney disease epidemiology collaboration; CMV, cytomegalovirus; eGFR, estimated glomerular filtration rate; EVR, everolimus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MDRD, modification of diet in renal disease; NODM, new onset diabetes mellitus; rTAC, reduced tacrolimus; tBPAR, treated biopsy proven acute rejection.