Table 1.
Outcomes of everolimus-based immunosuppressant for de-novo liver transplantation recipients in prospective randomised controlled trial
| Ref. | Treatment group | Time (d) from transplant EVR was initiated | Key inclusion and exclusion criteria | n | Follow-up period (mo) | Efficacy | Mean improvement in eGFR (mL/min per 1.73 m2) | Safety |
| Fischer et al[13] 2012 (PROTECT Study) | EVR + eliminate CNI by month 4 (EVR C0 5-12 ng/mL, if with CsA, EVR C0 8-12 ng/mL) | from day 30 and by day 56 | Inclusion: No rejection 2 wk before study, renal function > 50 mL/min | 101 | 12 | BPAR, graft loss or death: 20.8% vs 20.4% (P = 1.0) | 7.8 (P = 0.021) | No HAT, no increased risk of delayed wound healing. Higher incidence of infections, leukopenia, hyperlipidemia, anemia, proteinuria and arterial hypertension in the EVR group |
| Control: FK or CsA | Exclusion: Severe systemic infections, total cholesterol≥ 9 mmo/L, TG > 8.5 mmol/L, significant renal dysfunction (eGFR < 50 mL/min) | 102 | ||||||
| Sterneck et al[14] 2014 (PROTECT Study, extended to 36 mo) | Same as above | From day 30 and by day 56 | 41 | 36 | BPAR, graft loss and death: 19.5% vs 2.5% (P = 0.029) at month 11 (baseline) | 9.4 (P = 0.053) | Peripheral edema and back pain were significantly higher in EVR group | |
| 40 | BPAR, graft loss and death: 4.9% vs 5.0% (P = 1.0) at month 36 | |||||||
| Sterneck et al[15] 2016 (PROTECT Study, extended to 59 mo) | Same as above | From day 30 and by day 56 | 41 | 59 | BPAR, graft loss and death: 9.8% vs 7.5% (P = 1.0) from month 11 to month 59 | 11.4 (P = 0.021) | Peripheral edema and back pain were significantly higher in EVR group | |
| 40 | ||||||||
| De Simone et al[16] 2012 (H2304 Study) | EVR + low FK (EVR C0 3-8 ng/mL and FK C0 3-5 ng/mL) | Day 30 | Inclusion: eGFR ≥ 30 mL/min, FK trough ≥ 8 ng/mL. | 245 | 12 | BPAR, graft loss or death: 6.5% in EVR group vs 9.5% in control group (P < 0.001) | 8.5 (P < 0.001) | Higher incidence of proteinuria, acute renal failure, hyperlipidemia, neutropenia, peripheral edema, stomatitis/mouth ulceration, and thrombocytopenia in the EVR group |
| FK elimination (EVR C0 3-8 ng/mL till month 4 then 6-10 ng/mL thereafter and FK elimination started at month 4 when EVR C0 6-10 ng/mL achieved | Patent hepatic artery and veins, absence of rejection | 231 | ||||||
| Control: FK (C0 8-12 ng/mL until month 4 and C0 6-10 ng/mL thereafter) | Exclusion: HCC not fulfill Milan criteria, receipt of antibody induction therapy proteinuria ≥ 1 g/24 h | 243 | ||||||
| Saliba et al[17] 2013 (H2304 Study, extended to 24 mo) | EVR + low FK (EVR C0 3-8 ng/mL and FK C0 3-5 ng/mL) | Day 30 | 245 | 24 | BPAR, graft loss or death: 10.3% in EVR group vs 12.5% in control group (P = 0.452) | 6.7 (P = 0.002) | No increased risk of wound healing. Higher incidence of proteinuria, acute renal failure, hyperlipidemia, neutropenia, peripheral edema, stomatitis/mouth ulceration, and thrombocytopenia in the EVR group | |
| 243 | ||||||||
| Fischer et al[18] 2015 (H2304 Study, extended to 36 mo) | Same as above | Day 30 | 106 | 36 | BPAR, graft loss and death: 11.5% vs 14.6% (P = 0.334) | 8.5 (P = 0.005) | Higher drop-out rate due to ADR and incidence of hyperlipidemia in EVR group | |
| 125 |
ADR: Adverse drug reaction; BPAR: Biopsy proven acute rejection; C0: Trough level; CNI: Calcineurin inhibitor; CsA: Cyclosporine; EVR: Everolimus; FK: Tacrolimus; eGFR: Based on Modification of Diet in Renal Disease (MDRD) 4.