Table 1 Objectives of the Calcineurin Inhibitor-Sparing (CIS) trial

Primary objective

To evaluate a CsA-based immunosuppressive regimen monitored by residual NFAT-regulated gene expression concerning reduction in cardiovascular risk assessed by the change in pulse wave velocity from baseline to six-month follow-up, compared to a CsA-based regimen monitored by CsA trough levels in renal allograft recipients

Secondary efficacy objectives

To evaluate, in treatment group:

- a composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death and loss to follow-up at Month 6

- Incidence of BPAR, graft loss, loss to follow-up or death at Month 6

- S-creatinine and cystatin C at Month 6.

- Renal allograft function (eGFR calculated by MDRD, Nankivell and Cockroft-Gault formulae) at Month 6

- Evolution of renal function (S-creatinine) over time by slope analysis

- Creatinine slope (1/serum creatinine versus time) including the treatment period between baseline and Month 6

Secondary safety objectives

To evaluate, in treatment group:

- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

- Incidence of AEs leading to discontinuation from the study

- Incidence of major cardiovascular events (myocardial infarction, apoplexy, peripheral arterial occlusive disease)

- Pulse wave velocity, aortic pulse pressure, aortic systolic pressure, aortic augmentation index, ejection duration, heart rate variability

- Changes in blood pressure (central and peripheral pulse pressure, systolic and diastolic, mean arterial blood pressure)

- Changes in antihypertensive medication (number of antihypertensives)

- Changes in lipids (cholesterol, LDL-, HDL-cholesterol, triglyceride) and lipid-lowering drugs

- Changes in glucose levels, HbA1c and antidiabetic therapy

- Changes in cardiovascular risk (for example Framingham score)

- Changes in CsA-induced side effects (for example hypertrichosis, gingival overgrowth)

- Incidence and severity of infections

- Incidence and severity of malignancies

- Changes in the quality of life assessed by the ESRD SCL™ questionnaire and SF12 questionnaire

Exploratory objectives

To explore the incidence of DSA in treatment group, and in relation to acute rejection, in a subset of patients at participating centres