Back to results

Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

Primary Purpose

Atrial Fibrillation or Pulmonary Embolism, Need of Long Term Oral Anticoagulation Therapy (OAT), Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Rivaroxaban or Marcumar

About this trial

This is an interventional basic science trial for Atrial Fibrillation or Pulmonary Embolism focused on measuring Coronary or Valvular Calcification, Agatston Score, Rivaroxaban, Coumarin, Oral Anticoagulation Therapy (OAT), Atrial Fibrillation, Pulmonary Embolism

Eligibility Criteria

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

Inclusion Criteria:

Male or female patient aged > 18 years
Need for long-term OAT according to current international guidelines for the treatment of atrial fibrillation (ACC/(American Heart Association [AHA]/ European Society of Cardiology [ESC]guidelines) and / or pulmonary embolism (ACCP/ESC guidelines).
Existent Coronary or Valvular Calcification, or both and an Agatston Score > 50 in at least one location as assessed by MSCT at Screening
The anticipated minimum life expectancy is18 months

Exclusion Criteria:

Patient has any clinical condition which does not allow initiation of long-term OAT including all contraindications such as hypersensitivity to active ingredient or other excipients, clinically relevant acute bleedings and all other risk circumstances according to Summary of Medicinal Product (SmPC) in which all warnings and preventive measures and precautions are described and have to be kept.
Hypersensitivity to active substances investigated or to any of the excipients
Patients had a previous coronary stent implantation in a way which makes coronary artery calcification scoring impossible or unreliable and no Valvular Calcification with Agatston Score > 50
Chronic kidney disease (CKD) Stage V (GFR <15 mL)
Liver disease with coagulopathy or other bleeding disorders including cirrhotic patients with Child Pugh B and C
Acute gastrointestinal diseases
Clinically significant active bleeding
Alcohol, opioids or drug abuse
Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
Patient is unwilling or unable to give informed consent
Patient is unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Participation in a parallel interventional clinical trial
Patient has been committed to an institution by legal or regulatory order
Pregnant or lactating women
Female patient capable of bearing children without highly effective methods of birth control
Patient receives concomitant treatment with strong concurrent Cytochrome P 450 3A4 (CYP3A4)- and P- glycoprotein (P-gp)- inhibitors, i.e. azole-antimycotics (ketoconazole, itraconazole) or human immunodeficiency virus (HIV) protease inhibitors
Neuraxial Anaesthesia or spinal/epidural puncture
Known Endocarditis
Known Lactose intolerance

Sites / Locations

Hospital Coburg, Med. Clinic II for Internal Medicine and Cardiology
University Hospital Aachen, Department of Cardiology
St.-Antonius-Hospital Eschweiler, Internal Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rivaroxaban

Marcumar

Arm Description

Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0.

Outcomes

Primary Outcome Measures

Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT)

To investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed. tomography scanning (MSCT) within one year follow-up

Secondary Outcome Measures

Serum chemistry including Matrix Gla Protein (MPG) level changes and Fetuin-A (baseline/ follow up)

Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD)

Progression of aortic calcification (aortic Agatston Score)

Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging)

Full Information

NCT ID

NCT02066662

First Posted

February 17, 2014

Last Updated

October 21, 2020

Sponsor

RWTH Aachen University

Collaborators

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT02066662

Brief Title

Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

Official Title

Influence of Rivaroxaban Compared to Vitamin K Antagonist Treatment Upon Development of Cardiovascular Calcification in Patients With Atrial Fibrillation and/ or Pulmonary Embolism (IRIVASC- Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

March 2020 (Actual)

Study Completion Date

March 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

RWTH Aachen University

Collaborators

Bayer

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The following trial hypothesis will be proved: In patients with atrial fibrillation and/ or pulmonary embolism standard anticoagulant treatment with coumadin/phenprocoumon is associated with accelerated coronary or valvular calcification as assessed by cardiac computed tomography compared to the new anticoagulant therapy with rivaroxaban.

Detailed Description

A multi center, prospective, controlled, open, randomized, interventional clinical trial blinded concerning outcome measurements with a two- arm parallel group design will be performed to investigate the association of rivaroxaban compared to coumadin/phenprocoumon treatment for OAT in patients with atrial fibrillation and / or pulmonary embolism regarding the development and progression of coronary artery calcification (CAC) and aortic valve calcification (AVC) as assessed by multi-slice spiral computed tomography scanning (MSCT) within one year follow-up. In total 190 patients (95 patients per treatment arm) with atrial fibrillation and/ or pulmonary embolism with the indication for oral anticoagulation therapy will be enrolled. After screening first cardiac CT scan will be performed in order to validate if calcium score is >50 which is an inclusion criteria. If the patient matches all other inclusion/exclusion criteria the remaining imaging procedures (Echocardiography, Intima Media Thickness of carotid artery (IMT) and Flow Mediated Vasodilatation (FMD), Electrocardiography (ECG) and blood pressure are executed. Pregnancy strip test will be executed and also serum chemistry, hematology, coagulation and batch analysis will be performed. Patients will then be randomized to one of the two arms (Rivaroxaban or Marcumar) and will undergo the same examinations and measurements as described above at 1 week, 1, 6, 9 and 12 month Follow- Up (FU). In case of a positive result in respect to the primary endpoint a FU after 2 years will be performed. Primary outcome measures will be assessed after all active patients will have completed 12-months study visit (interim analysis)

6. Conditions and Keywords

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

Atrial Fibrillation or Pulmonary Embolism, Need of Long Term Oral Anticoagulation Therapy (OAT), Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location

Keywords

Coronary or Valvular Calcification, Agatston Score, Rivaroxaban, Coumarin, Oral Anticoagulation Therapy (OAT), Atrial Fibrillation, Pulmonary Embolism

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

192 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rivaroxaban

Arm Type

Experimental

Arm Description

Arm Title

Marcumar

Arm Type

Active Comparator

Arm Description

Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0.

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban or Marcumar

Other Intervention Name(s)

Xarelto; Marcumar

Intervention Description

Arm A: Rivaroxaban (tablet) for patients with atrial fibrillation: with 20 mg once daily for patients with eGFR > 49 ml per minute and 15 mg rivaroxaban once daily for patients with eGFR of 15 to 49 ml. Rivaroxaban (tablet) for patients with pulmonary embolism : 2x a day 15 mg at day 1-21 and 1x 20 mg from day 22 ongoing; Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0.

Primary Outcome Measure Information:

Title

Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT)

Description

Time Frame

Cardiac Computertomography (CT) will be performed at screening, after 12 months and at 24 months

Secondary Outcome Measure Information:

Title

Serum chemistry including Matrix Gla Protein (MPG) level changes and Fetuin-A (baseline/ follow up)

Time Frame

baseline and 12 month Follow Up

Title

Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD)

Time Frame

Baseline, 6, 12 and 24 month FU

Title

Progression of aortic calcification (aortic Agatston Score)

Time Frame

screening and 12 month FU

Title

Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging)

Time Frame

baseline, 6, 9, 12 and 24 month FU

Other Pre-specified Outcome Measures:

Title

Occurrence of major cardiovascular complications (MACE)

Time Frame

1 week, 1, 6, 9, 12 and 24 month FU

Title

Non- major bleedings

Time Frame

1week, 1, 6, 9, 12 and 24 month FU

Title

Major bleedings

Time Frame

1 week, 6, 9, 12 and 24 month FU

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female patient aged > 18 years Need for long-term OAT according to current international guidelines for the treatment of atrial fibrillation (ACC/(American Heart Association [AHA]/ European Society of Cardiology [ESC]guidelines) and / or pulmonary embolism (ACCP/ESC guidelines). Existent Coronary or Valvular Calcification, or both and an Agatston Score > 50 in at least one location as assessed by MSCT at Screening The anticipated minimum life expectancy is18 months Exclusion Criteria: Patient has any clinical condition which does not allow initiation of long-term OAT including all contraindications such as hypersensitivity to active ingredient or other excipients, clinically relevant acute bleedings and all other risk circumstances according to Summary of Medicinal Product (SmPC) in which all warnings and preventive measures and precautions are described and have to be kept. Hypersensitivity to active substances investigated or to any of the excipients Patients had a previous coronary stent implantation in a way which makes coronary artery calcification scoring impossible or unreliable and no Valvular Calcification with Agatston Score > 50 Chronic kidney disease (CKD) Stage V (GFR <15 mL) Liver disease with coagulopathy or other bleeding disorders including cirrhotic patients with Child Pugh B and C Acute gastrointestinal diseases Clinically significant active bleeding Alcohol, opioids or drug abuse Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study Patient is unwilling or unable to give informed consent Patient is unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study Participation in a parallel interventional clinical trial Patient has been committed to an institution by legal or regulatory order Pregnant or lactating women Female patient capable of bearing children without highly effective methods of birth control Patient receives concomitant treatment with strong concurrent Cytochrome P 450 3A4 (CYP3A4)- and P- glycoprotein (P-gp)- inhibitors, i.e. azole-antimycotics (ketoconazole, itraconazole) or human immunodeficiency virus (HIV) protease inhibitors Neuraxial Anaesthesia or spinal/epidural puncture Known Endocarditis Known Lactose intolerance

Facility Information:

Facility Name

Hospital Coburg, Med. Clinic II for Internal Medicine and Cardiology

City

Coburg

State/Province

Bavaria

ZIP/Postal Code

96450

Country

Germany

Facility Name

University Hospital Aachen, Department of Cardiology

City

Aachen

State/Province

North Rhine Westphalia

ZIP/Postal Code

52074

Country

Germany

Facility Name

St.-Antonius-Hospital Eschweiler, Internal Medicine

City

Eschweiler

State/Province

North Rhine Westphalia

ZIP/Postal Code

52249

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

We'll reach out to this number within 24 hrs