Vitamin K1 to slow vascular calcification in hemodialysis patients (VitaVasK)

Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular
mortality associated with extensive vascular calcification (VC). This offers an
* at least partial * explanation for the excessively increased cardiovascular
mortality in this population. In the past years, the development of VC was
discovered to be actively regulated and influenced by inhibitors of
calcification (e.g. matrix Gla protein). Matrix Gla protein (MGP) is a powerful
vascular wall-based inhibitor of VC. MGP is produced by vascular smooth muscle
cells and requires post-translational modification by vitamin K-dependent gamma
carboxylation to be fully active. We are still lacking data supporting the
hypothesis that vitamin K supplementation may slow down the progression of VC
in HD patients. All HD patients exhibit insufficient carboxylation activity
and must be considered vitamin K deficient. Together with the increased VC,
they represent an ideal population for interventional trials involving the
vitamin K system. In this trial, we also observed that all dialysis patients
included had insufficient vitamin K serum levels, indicating that there was no
substantial influence of food intake on vitamin K deficiency. In addition, this
demonstrates that all patients have vitamin K levels that are too insufficient
to allow adequate MGP carboxylation.

The aim of the study is to show that a therapy based on a thrice weekly
administration (i.e. at each HD session) of vitamin K1 for a period of 18
months attenuates the progression of coronary artery and thoracic aortic
calcifications compared to standard treatment. Furthermore, we want to analyse
whether the thrice weekly intake (i.e. at each HD session) of vitamin K1 for 18
months leads to an attenuation of the calcification of aortic and mitral valve
and reduction of major adverse cardiovascular events (MACE, i.e. sum of
myocardial infarction, acute coronary syndrome, symptom-driven
revascularization, stroke, embolism, cardiovascular death) all-cause mortality
and plasma level of dpucMGP and an increase in the plasma level of dpcMGP.

The VitaVasK study is a prospective, randomised, multicenter, multinational,
controlled clinical trial using a two-arm parallel group design

After randomisation, the patient will be treated with Vitamin K1 for 18 months,
or the patient won't be treated with Vitamine K1. 3 Visits will take place in
these 18 months, where the patient will get a CT scan, physical examination and
bloodsamples will be taken. After 36 months and 60 months telephone interviews
will take place.

The dose of vitamin K1 being administered orally (5 mg) has been previously
tested, in some cases in much higher doses, and has it been deemed safe and is
well tolerated with hardly any adverse effects. Treatment with vitamin K1 is
not known to show undesirable effects or discomfort. Moreover, in the scope of
this clinical research, certain risks or undesirable effects that may cause
some discomfort may be involved in study-related measures. Relatively minimal
risks are to be anticipated, for example, in the blood draws, since merely a
small amount of blood is required (each time approximately 18 mL) and the
method for blood draw (due to dialysis) would require no additional puncture.
Beyond this, the three planned CT examinations carry the risk of exposure to
radiation. The radiation exposure from the CTs equals your annual background
exposure (ca. 2.1 mSv).