Clinical trial NCT02610933: Effect on Vascular Calcification of Replacing Warfarin by Rivaroxaban With or Without VitK2 in Hemodialysis Patients
Official title: The Effect of Replacement of Vitamin K Antagonist by Rivaroxaban With or Without Vitamin K2 Supplementation on Vascular Calcifications in Chronic Hemodialysis Patients: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vascular Calcification
Keywords: vascular calcification
hemodialysis
rivaroxaban
vitamin K2
Lead sponsor: Onze Lieve Vrouw Hospital
Sponsor class: OTHER
First posted: 2015-11-20
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: absolute and relative change in coronary artery calcification score
timeFrame: 18 months
measure: absolute and relative change in thoracic aortic calcification score
timeFrame: 18 months
measure: absolute and relative change in pulse wave velocity
timeFrame: 18 months
Secondary outcomes:
measure: absolute and relative change in aortic valve calcification score
timeFrame: 18 months
measure: absolute and relative change in mitral valve calcification score
timeFrame: 18 months
measure: mortality from any cause
timeFrame: 18 months
measure: myocardial infarction, acute coronary syndrome, symptom-driven coronary revascularization and death from cardiovascular cause
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
measure: Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: OLV Hospital
Study officials:
affiliation: Nephrology Department OLV Hospital Aalst Belgium
name: Rogier Caluwé, MD
role: PRINCIPAL_INVESTIGATOR
References: