Vascular Calcification
Conditions
Keywords
vascular calcification, hemodialysis, rivaroxaban, vitamin K2
Brief summary
This study examines patients on chronic hemodialysis with non-valvular atrial fibrillation, who have a CHA2DS2-VASc Score of ≥ 2 and therefore are candidates for or already receive a vitamin K antagonist. The first question is whether replacement of the vitamin K antagonist by rivaroxaban is able to slow progression of vascular calcification. The second question is whether addition of vitamin K2 to rivaroxaban can further slow down or even halt the progression of vascular calcification.
Detailed description
The present study targets dialysis patients with non-valvular atrial fibrillation requiring treatment with vitamin K antagonists. It addresses the question whether replacement of the vitamin K antagonist by rivaroxaban is able to slow progression of vascular calcification (VC). The second research question is whether addition of vitamin K2 to rivaroxaban can further beneficially affect the progression of VC. Two non-invasive methods are used to evaluate the impact of interventions on the progression of VC: i.e. coronary artery calcification (CAC) and pulse wave velocity (PWV) measurements. The detection of CAC is predictive for the presence of obstructive coronary artery disease and future coronary events. VC and stiffening of the central elastic-type arteries are independent predictors of cardiovascular morbidity and mortality in hemodialysis patients.
Interventions
DRUGrivaroxaban
replacement of vitamin K antagonist by rivaroxaban
DIETARY_SUPPLEMENTVitamin K2
Vitamin K2 supplementation
Sponsors
Onze Lieve Vrouw Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* end stage renal failure treated with chronic hemodialysis * atrial fibrillation * CHA2DS2-VASc Score ≥ 2 * ability to provide informed consent
Exclusion criteria
* known intestinal malabsorption or inability to take oral medication * inability to stop co-medication that causes major interactions with rivaroxaban (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, ritonavir, rifampicin, phenytoin, carbamazepine, phenobarbital or St John's wort) * investigator's assessment that the subject's life expectancy is less than 1 year * prosthetic mechanical heart valve * contraindication for anticoagulation * liver dysfunction Child-Pugh grade B-C * pregnancy, breastfeeding, inadequate contraception * incompliance with medication and scheduled investigations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| absolute and relative change in coronary artery calcification score | 18 months | score measured by unenhanced electrocardiographically-gated CT of the heart and thoracic aorta and calculated on 2.5 mm slices using Smartscore v.4.0 (GE Healthcare) |
| absolute and relative change in thoracic aortic calcification score | 18 months | score measured by unenhanced electrocardiographically-gated CT of the heart and thoracic aorta and calculated on 2.5 mm slices using Smartscore v.4.0 (GE Healthcare) |
| absolute and relative change in pulse wave velocity | 18 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| myocardial infarction, acute coronary syndrome, symptom-driven coronary revascularization and death from cardiovascular cause | 18 months | — |
| Stroke, defined as sudden onset of focal neurological deficit consistent with the territory of a major cerebral artery and categorised as ischaemic, haemorrhagic, or unspecified. | 18 months | — |
| absolute and relative change in aortic valve calcification score | 18 months | score measured by unenhanced electrocardiographically-gated CT of the heart and thoracic aorta and calculated on 2.5 mm slices using Smartscore v.4.0 (GE Healthcare) |
| Major bleeding, defined as a requirement for transfusion of two or more units of blood or a decrease in haemoglobin of 2 g/dL or more. | 18 months | — |
| Life-threatening bleeding, defined as fatal bleeding, symptomatic intracranial bleeding, a decrease in haemoglobin of 5 g/dL or more, or a requirement for transfusion of four or more units of blood, inotropic agents, or surgery. | 18 months | — |
| Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy. | 18 months | — |
| absolute and relative change in mitral valve calcification score | 18 months | score measured by unenhanced electrocardiographically-gated CT of the heart and thoracic aorta and calculated on 2.5 mm slices using Smartscore v.4.0 (GE Healthcare) |
| mortality from any cause | 18 months | — |
Countries
Belgium
Outcome results
None listed