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Effect on Vascular Calcification of Replacing Warfarin by Rivaroxaban With or Without VitK2 in Hemodialysis Patients

Phase 4
Completed
Conditions
Vascular Calcification
Interventions
Dietary Supplement: Vitamin K2
Registration Number
NCT02610933
Lead Sponsor
Onze Lieve Vrouw Hospital
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
117
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
rivaroxabanrivaroxabanRivaroxaban 10 mg tablet by mouth once daily for 18 months
rivaroxaban and vitamin K2rivaroxabanRivaroxaban 10 mg tablet by mouth once daily and MK-7 2000 microgram tablet by mouth thrice weekly for 18 months
rivaroxaban and vitamin K2Vitamin K2Rivaroxaban 10 mg tablet by mouth once daily and MK-7 2000 microgram tablet by mouth thrice weekly for 18 months
Primary Outcome Measures
NameTimeMethod
absolute and relative change in coronary artery calcification score18 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 score18 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 velocity18 months
Secondary Outcome Measures
NameTimeMethod
absolute and relative change in aortic valve calcification score18 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 mitral valve calcification score18 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 cause18 months
myocardial infarction, acute coronary syndrome, symptom-driven coronary revascularization and death from cardiovascular cause18 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
Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy.18 months
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

Trial Locations

Locations (1)

OLV Hospital

🇧🇪

Aalst, Belgium

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