ADHERE: randomized controlled trial comparing renal function inde novokidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus

Abstract

SUMMARYADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolongedrelease tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m 2 ; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2). 2017; 30: 83-95 Transplant International

Long‐term, prolonged‐release tacrolimus‐based immunosuppression in de novo kidney transplant recipients: 5‐year prospective follow‐up of the ADHERE study patients

“…Overall, 16 patients (2.7%) had ADRs that were considered probably tacrolimus‐related during follow‐up. These safety findings are consistent with those from the primary ADHERE study and no new safety signals beyond the established safety profile for tacrolimus were detected in this kidney transplant patient population.…”

“…ADHERE (ClinicalTrials.gov identifier: NCT01363752) was a multicenter, randomized, open‐label, parallel‐group, 52‐week, Phase IV study that evaluated renal function in de novo adult kidney transplant patients treated with once‐daily prolonged‐release tacrolimus (Advagraf ® ; Astellas Pharma Europe BV, Leiden, the Netherlands) plus MMF or sirolimus . Eligible patients were aged 18 years or over, with end‐stage kidney disease, suitable for primary renal transplantation or re‐transplantation (unless the graft was lost from rejection within 6 months) and who received a kidney transplant from a deceased or living donor.…”

“…Eligible patients were aged 18 years or over, with end‐stage kidney disease, suitable for primary renal transplantation or re‐transplantation (unless the graft was lost from rejection within 6 months) and who received a kidney transplant from a deceased or living donor. Full study design details and inclusion/exclusion criteria of ADHERE were described previously .…”

“…Post randomization, Arm 1 tacrolimus target trough levels were 8–12 ng/ml on Days 28–41, and 6–10 ng/ml from Day 42 to 1 year. In Arm 2, tacrolimus target trough levels were 8–12 ng/ml on Days 28–41; from Day 42 to 1 year, the tacrolimus dose was then decreased by ≥25% to target tacrolimus trough levels of 4–5 ng/ml . In the follow‐up study, patients received prolonged‐release or immediate‐release tacrolimus.…”

“…The ADHERE study was a 12‐month, randomized, open‐label, Phase IV study that compared renal function in de novo kidney transplant recipients receiving prolonged‐release tacrolimus in combination with either MMF (Arm 1) or sirolimus (Arm 2) . Renal function was found to be comparable between the two arms at 12 months post‐transplant, with an acceptable tolerability profile.…”