A Prospective, Pilot Trial to Evaluate Safety and Tolerability of Everolimus for the Prevention of BK and CMV Viremia in HLA Sensitized Kidney Transplant Recipients

Detailed Summary

A growing number of patients on the kidney transplant waiting list are broadly human leukocyte antigen (HLA) sensitized (HS). These patients are unlikely to have a compatible donor. Therefore they wait longer and have increased morbidity and mortality. Desensitization with intravenous immune globulin (IVIG) and rituximab with alemtuzumab induction improves transplant rates and achieves good allograft outcomes. However, HS patients are at risk for viral infections after transplant. We have previously shown an increased incidence of BKV infections after desensitization with HS patients having higher peak viral loads. Cytomegalovirus (CMV) and polyomavirus BK (BKV) infections place HS renal transplant recipients at particular risk. Allograft rejection is associated with both CMV and BKV infection. This is of particular concern for HS patients as they are at an increased risk of rejection at baseline. Furthermore, the frequent development of leukopenia after transplantation often requires the CMV prophylactic agent to be discontinued along with lowering immunosuppression. This increases the risk of CMV infection and allograft rejection. Everolimus was approved for rejection prophylaxis in combination with calcineurin inhibitors (CNI). CNI used in the study that led to drug's approval was cyclosporine. There are several trials nearing it's completion that utilize low dose tacrolimus instead. In 2012 Novartis published data from several trials showing superior outcomes using everolimus + low dose tacrolimus. This combination is currently approved in EU. It is also a combination that is standard of care (SOC) at our center for patients on everolimus. This study aims to demonstrate that use of everolimus as part of a maintenance immunosuppression regimen may decrease viral infections without lowering overall immunosuppression thus improving allograft function and survival.

Study Details

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Interventions