TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Ahlenstiel-Grunow, Thurid A1 - Koch, Armin A1 - Großhennig, Anika A1 - Frömke, Cornelia A1 - Sester, Martina A1 - Sester, Urban A1 - Schröder, Christoph A1 - Pape, Lars T1 - A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial JF - Trials N2 - Background: After kidney transplantation, immunosuppressive therapy causes impaired cellular immune defense leading to an increased risk of viral complications. Trough level monitoring of immunosuppressants is insufficient to estimate the individual intensity of immunosuppression. We have already shown that virus-specific T cells (Tvis) correlate with control of virus replication as well as with the intensity of immunosuppression. The multicentre IVIST01-trial should prove that additional steering of immunosuppressive and antiviral therapy by Tvis levels leads to better graft function by avoidance of over-immunosuppression (for example, viral infections) and drug toxicity (for example, nephrotoxicity). Methods/design: The IVIST-trial starts 4 weeks after transplantation. Sixty-four pediatric kidney recipients are randomized either to a non-intervention group that is only treated conservatively or to an intervention group with additional monitoring by Tvis. The randomization is stratified by centre and cytomegalovirus (CMV) prophylaxis. In both groups the immunosuppressive medication (cyclosporine A and everolimus) is adopted in the same target range of trough levels. In the non-intervention group the immunosuppressive therapy (cyclosporine A and everolimus) is only steered by classical trough level monitoring and the antiviral therapy of a CMV infection is performed according to a standard protocol. In contrast, in the intervention group the dose of immunosuppressants is individually adopted according to Tvis levels as a direct measure of the intensity of immunosuppression in addition to classical trough level monitoring. In case of CMV infection or reactivation the antiviral management is based on the individual CMV-specific immune defense assessed by the CMV-Tvis level. Primary endpoint of the study is the glomerular filtration rate 2 years after transplantation; secondary endpoints are the number and severity of viral infections and the incidence of side effects of immunosuppressive and antiviral drugs. Discussion: This IVIST01-trial will answer the question whether the new concept of steering immunosuppressive and antiviral therapy by Tvis levels leads to better future graft function. In terms of an effect-related drug monitoring, the study design aims to realize a personalization of immunosuppressive and antiviral management after transplantation. Based on the IVIST01-trial, immunomonitoring by Tvis might be incorporated into routine care after kidney transplantation. KW - kidney transplantation KW - immunosuppression KW - virus-specific T cells KW - personalized immunosuppressive therapy KW - viral infections KW - pediatric transplantation KW - cytomegalovirus KW - antiviral therapy KW - over-immunosuppression KW - immunomonitoring KW - drug-monitoring Y1 - 2014 UN - https://nbn-resolving.org/urn:nbn:de:1111-2016050235305 U6 - https://doi.org/10.25968/opus-1123 DO - https://doi.org/10.25968/opus-1123 VL - 2014 IS - 15:324 ER -