Comparing daytime plasma levels of rivaroxaban with a morning versus evening dose

Currently, no specific recommendations are made for the timing of intake of
rivaroxaban in patients treated for venous thrombo-embolism. In clinical
practice this means that patients are advised to take rivaroaxaban with either
breakfast or supper. As rivaroxaban is accompanied by a bleeding risk,
specifically in the case of trauma and emergency invasive procedures, the
lowest plasma-levels should preferably occur during daytime. This could be
achieved by an evening dose rather than an morning dose. However, it remains
unclear whether plasma levels of an evening dose are relevantly more lower than
from a morning dose and whether the achieved plasma levels are adequately low
enough to perform invasive procedures safely.

To determine and compare plasma levels of rivaroxaban during daytime with a
morning and evening intake in patients treated for venous thromboembolism

Crossover study

We will ask eligible subjects informed consent for participation in this study.
Subjects will not benefit from participation to this study. However, the burden
and risk of this study are considered limited. First, subjects wil be asked to
keep a diary of dietary pattern and timing of rivaroxaban intake. This diary is
not detailed and is mostly focused on ticking boxes. Secondly, we will change
dose-timing by prolonging or shortening the dosing interval with 6 hours in two
steps. We do not expect complications from this temporary change in dosing
interval, as this is method is used in clinical practice to adjust dose-timing
for clinical or patient's personal reasons. Lastly, we will sample 6x7 mL blood
by a venous puncture. Besides discomfort from the puncture, we are not aware of
any risks or harms of this blood sampling. The results of this study may
contribute to improving the safety of anticoagulation therapy.