The Calcineurin Inhibitor-Sparing (CIS) Trial - individualised calcineurin-inhibitor treatment by immunomonitoring in renal allograft recipients protocol for a randomised controlled trial

TY - JOUR

T1 - The Calcineurin Inhibitor-Sparing (CIS) Trial - individualised calcineurin-inhibitor treatment by immunomonitoring in renal allograft recipients protocol for a randomised controlled trial

AU - Sommerer, Claudia

AU - Schaier, Matthias

AU - Morath, Christian

AU - Schwenger, Vedat

AU - Rauch, Geraldine

AU - Giese, Thomas

AU - Zeier, Martin

PY - 2014/12/13

Y1 - 2014/12/13

N2 - BACKGROUND: Adequate monitoring tools are required to optimise the immunosuppressive therapy of an individual patient. Particularly, in calcineurin inhibitors, as critical dose drugs with a narrow therapeutic range, the optimal monitoring strategies are discussed in terms of safety and efficacy. Nevertheless, no pharmacokinetic monitoring markers reflect the biological activity of the drug. A new quantitative analysis of gene expression was employed to directly measure the functional effects of calcineurin inhibition: the transcriptional activities of the nuclear factor of activated T-cell (NFAT)-regulated genes in the peripheral blood.METHODS/DESIGN: The CIS study is a randomised prospective controlled trial, comparing a ciclosporin A (CsA)-based immunosuppressive regimen monitored by CsA trough levels to a CsA-based immunosuppressive regimen monitored by residual NFAT-regulated gene expression. Pulse wave velocity as an accepted surrogate marker of the cardiovascular risk is assessed in both study groups. Our hypothesis is that an individualised CsA therapy monitored by residual NFAT-regulated gene expression results in a significantly lower cardiovascular risk compared to CsA therapy monitored by CsA trough levels.DISCUSSION: There is a lack of evidence in individualising standard immunosuppression in renal allograft recipients. The CIS study will consider the feasibility of individualised ciclosporin A immunosuppression by pharmacodynamic monitoring and evaluate the opportunity to reduce cardiovascular risk while maintaining sufficient immunosuppression.TRIAL REGISTRATION: EudraCT identifier 2011-003547-21, registration date 18 July 2011https://www.clinicaltrialsregister.eu.

AB - BACKGROUND: Adequate monitoring tools are required to optimise the immunosuppressive therapy of an individual patient. Particularly, in calcineurin inhibitors, as critical dose drugs with a narrow therapeutic range, the optimal monitoring strategies are discussed in terms of safety and efficacy. Nevertheless, no pharmacokinetic monitoring markers reflect the biological activity of the drug. A new quantitative analysis of gene expression was employed to directly measure the functional effects of calcineurin inhibition: the transcriptional activities of the nuclear factor of activated T-cell (NFAT)-regulated genes in the peripheral blood.METHODS/DESIGN: The CIS study is a randomised prospective controlled trial, comparing a ciclosporin A (CsA)-based immunosuppressive regimen monitored by CsA trough levels to a CsA-based immunosuppressive regimen monitored by residual NFAT-regulated gene expression. Pulse wave velocity as an accepted surrogate marker of the cardiovascular risk is assessed in both study groups. Our hypothesis is that an individualised CsA therapy monitored by residual NFAT-regulated gene expression results in a significantly lower cardiovascular risk compared to CsA therapy monitored by CsA trough levels.DISCUSSION: There is a lack of evidence in individualising standard immunosuppression in renal allograft recipients. The CIS study will consider the feasibility of individualised ciclosporin A immunosuppression by pharmacodynamic monitoring and evaluate the opportunity to reduce cardiovascular risk while maintaining sufficient immunosuppression.TRIAL REGISTRATION: EudraCT identifier 2011-003547-21, registration date 18 July 2011https://www.clinicaltrialsregister.eu.

KW - Calcineurin Inhibitors

KW - Clinical Protocols

KW - Cyclosporine

KW - Drug Monitoring

KW - Gene Expression Regulation

KW - Germany

KW - Graft Rejection

KW - Graft Survival

KW - Humans

KW - Immunosuppressive Agents

KW - Kidney Transplantation

KW - Monitoring, Immunologic

KW - NFATC Transcription Factors

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Pulse Wave Analysis

KW - Research Design

KW - Time Factors

KW - Treatment Outcome

KW - Comparative Study

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/1745-6215-15-489

DO - 10.1186/1745-6215-15-489

M3 - SCORING: Journal article

C2 - 25494823

VL - 15

SP - 489

JO - TRIALS

JF - TRIALS

SN - 1745-6215

ER -