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

Primary Purpose

Vascular Calcification

Status

Completed

Phase

Phase 4

Locations

Belgium

Study Type

Interventional

Intervention

rivaroxaban

Vitamin K2

About this trial

This is an interventional prevention trial for Vascular Calcification focused on measuring vascular calcification, hemodialysis, rivaroxaban, vitamin K2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

OLV Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Active Comparator

Arm Label

Vitamin K antagonist

rivaroxaban

rivaroxaban and vitamin K2

Arm Description

Vitamin K antagonist treatment targeting an international normalized ratio of 2 to 3 for 18 months

Rivaroxaban 10 mg tablet by mouth once daily for 18 months

Rivaroxaban 10 mg tablet by mouth once daily and MK-7 2000 microgram tablet by mouth thrice weekly for 18 months

Outcomes

Primary Outcome Measures

absolute and relative change in coronary artery calcification score

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

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

Secondary Outcome Measures

absolute and relative change in aortic valve calcification score

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 score

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

myocardial infarction, acute coronary syndrome, symptom-driven coronary revascularization and death from cardiovascular cause

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.

Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy.

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.

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.

Full Information

NCT ID

NCT02610933

First Posted

November 16, 2015

Last Updated

January 25, 2019

Sponsor

Onze Lieve Vrouw Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02610933

Brief Title

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

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

November 2015 (undefined)

Primary Completion Date

January 23, 2019 (Actual)

Study Completion Date

January 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Onze Lieve Vrouw Hospital

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Vascular Calcification

Keywords

vascular calcification, hemodialysis, rivaroxaban, vitamin K2

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

117 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vitamin K antagonist

Arm Type

No Intervention

Arm Description

Vitamin K antagonist treatment targeting an international normalized ratio of 2 to 3 for 18 months

Arm Title

rivaroxaban

Arm Type

Active Comparator

Arm Description

Rivaroxaban 10 mg tablet by mouth once daily for 18 months

Arm Title

rivaroxaban and vitamin K2

Arm Type

Active Comparator

Arm Description

Rivaroxaban 10 mg tablet by mouth once daily and MK-7 2000 microgram tablet by mouth thrice weekly for 18 months

Intervention Type

Drug

Intervention Name(s)

rivaroxaban

Intervention Description

replacement of vitamin K antagonist by rivaroxaban

Intervention Type

Dietary Supplement

Intervention Name(s)

Vitamin K2

Other Intervention Name(s)

MK-7

Intervention Description

Vitamin K2 supplementation

Primary Outcome Measure Information:

Title

absolute and relative change in coronary artery calcification score

Description

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)

Time Frame

18 months

Title

absolute and relative change in thoracic aortic calcification score

Description

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)

Time Frame

18 months

Title

absolute and relative change in pulse wave velocity

Time Frame

18 months

Secondary Outcome Measure Information:

Title

absolute and relative change in aortic valve calcification score

Description

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)

Time Frame

18 months

Title

absolute and relative change in mitral valve calcification score

Description

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)

Time Frame

18 months

Title

mortality from any cause

Time Frame

18 months

Title

myocardial infarction, acute coronary syndrome, symptom-driven coronary revascularization and death from cardiovascular cause

Time Frame

18 months

Title

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.

Time Frame

18 months

Title

Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy.

Time Frame

18 months

Title

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.

Time Frame

18 months

Title

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rogier Caluwé, MD

Organizational Affiliation

Nephrology Department OLV Hospital Aalst Belgium

Official's Role

Principal Investigator

Facility Information:

Facility Name

OLV Hospital

City

Aalst

ZIP/Postal Code

9300

Country

Belgium

12. IPD Sharing Statement

Learn more about this trial

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

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