Very early introduction of everolimus in de novo liver transplantation: results of a multicenter, prospective, randomized trial (EPOCAL).Cillo, U., Saracino, L. et al.
Liver Transpl, 2018;[record in progress].
To determine the efficacy and safety of an early (postoperative day 7) everolimus initiation and minimized tacrolimus compared with the standard tacrolimus regimen after lung transplantation.
Following one week after transplantation, patients were randomized (2:1) to receive everolimus and to gradually minimize or withdraw tacrolimus when everolimus was stable at >5 ng/mL, or to continue tacrolimus at 6‐12 ng/mL.
140 participants were enrolled into this study (18-70 years): 93 randomized in the EVR group and 47 in the control group.
The primary endpoint was the number of patients who did not show a treated biopsy-proven acute rejection (tBPAR) after 3 months from transplantation. Secondary outcomes included, composite efficacy failure rate at 3, 12 and 24 months post-transplantation and renal function (assessed by eGFR) at 1, 6, 12 and 24 months.
Up to 24 months
This multi-centre RCT was conducted in early, stable liver transplant recipients in an effort to minimise the complications of calcineurin inhibitors. The exact method of randomisation is not described and the study was not blinded due to having to dose-adjust the medications. The power calculation was conducted on the basis of randomising patients in a 2:1 ratio and with assumed inactivity cutoff for the treatment of <60% and activity cutoff of >75%. As it happens, the rate of treated-BPAR was 12.9% in the everolimus group and 4.3% in the control group. This was reported as not a statistically significant difference (p=0.09), but if this difference in acute rejection were real, then this represents a clinically significant difference that this study was underpowered to see. A significant number of patients (17, 12.1%) were withdrawn during the first 3 months. 20 of the patients in the everolimus arm minimised tacrolimus doses before reaching their target everolimus dose and therefore were potentially under-immunosuppressed. Graft and patient survival was similar at 12 months. Conversion to everolimus was associated with a much higher rate of incisional hernia (25.8% versus 6.3%), wound complications (18.2% versus 0%) and higher rate of hypercholesterolaemia (15% versus 6.3%), but with much improved GFR over follow up, fewer neurological disorders (13.9% versus 31.9%) and serious infections (11.8% versus 27.6%).
Clinicaltrials.gov - NCT01423708