Comparison of an Innovative Everolimus-Containing Quadruple Immunosuppressive Regimen Versus a Standard Triple Regimen in Lung Transplant Recipients and Its Impact on Renal Function, Safety and Efficacy: The 4EVERLUNG Study Design

Purpose Data from previous studies show that everolimus can facilitate CNI minimization with comparable efficacy and safety, while simultaneously reducing CNI-induced chronic nephropathy in transplant recipients. The 4EVERLUNG study (NCT01404325) aims to evaluate the impact of a “quadruple low” immunosuppressive regimen on renal function, safety and efficacy in lung transplant recipients (LTxR). Methods and Materials 4EVERLUNG is a multi-center, randomized, controlled, open-label trial. Overall, 232 LTxR will be randomized to receive either Everolimus (C 0-h 4±1ng/mL) + reduced CNI (Tac C 0h 3-5ng/mL or CsA C 0h 50±25ng/mL) + MPA + steroids or standard CNI (Tac C 0h >5ng/mL or CsA C 0h >100ng/mL) + MPA + steroids. Everolimus introduction and CNI reduction in the “quadruple low” arm should be achieved latest within two weeks post randomization. One primary objective is to demonstrate superior renal function after partial substitution of CNIs by Everolimus 12 months post randomization. Moreover, significant inhibition of the progression of bronchiolitis obliterans syndrom (BOS) could be an effect by using Everolimus. Key secondary objectives at the end of study include non-inferior efficacy (BPAR, graft loss, death), safety (infections, hypertension, hyperlipidemia) and evaluation of the patient’s quality of life (QoL, SF36). Results Recruitment started in Feb 2012, whereas 21 patients at seven transplantation centers have been randomized in 4EVERLUNG until Nov 2012. Conclusions Reducing CNI-dependent side effects such as chronic allograft nephropathy, which contribute to fatal long-term outcomes after Tx, represent one of the most pressing issues in transplantation. The results of 4EVERLUNG might therefore contribute to evaluate the benefit of an innovative “quadruple low” immunosuppressive regimen in LTxR by preserving renal function and/or limiting progression of BOS.