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Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

This study is currently recruiting participants.
Verified August 2017 by RWTH Aachen University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02066662
First Posted: February 19, 2014
Last Update Posted: August 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Bayer
Information provided by (Responsible Party):
RWTH Aachen University
  Purpose
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.

Condition Intervention Phase
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 Drug: Rivaroxaban or Marcumar Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
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)

Resource links provided by NLM:


Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:
  • Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT) [ Time Frame: Cardiac Computertomography (CT) will be performed at screening, after 12 months and optional at 24 months ]
    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) [ Time Frame: baseline and 12 month Follow Up ]
  • 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 ]
  • Progression of aortic calcification (aortic Agatston Score) [ Time Frame: screening and 12 month FU ]
  • 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 Outcome Measures:
  • Occurrence of major cardiovascular complications (MACE) [ Time Frame: 1 week, 1, 6, 9, 12 and 24 month FU ]
  • Non- major bleedings [ Time Frame: 1week, 1, 6, 9, 12 and 24 month FU ]
  • Major bleedings [ Time Frame: 1 week, 6, 9, 12 and 24 month FU ]

Estimated Enrollment: 253
Study Start Date: July 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban
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
Drug: Rivaroxaban or Marcumar

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.

Other Name: Xarelto; Marcumar
Active Comparator: Marcumar
Arm B: Adjusted dose coumadin/phenprocoumon (tablet) titrated according to target international normalized ratio (INR) with a target range 2.0 to 3.0.
Drug: Rivaroxaban or Marcumar

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.

Other Name: Xarelto; Marcumar

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 253 patients (126 patients per treatment arm including calculated drop outs and invalid cases) 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 optionally.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patient aged > 18 years
  2. 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).
  3. Existent Coronary or Valvular Calcification, or both and an Agatston Score > 50 in at least one location as assessed by MSCT at Screening
  4. The anticipated minimum life expectancy is18 months

Exclusion Criteria:

  1. 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.
  2. Hypersensitivity to active substances investigated or to any of the excipients
  3. Patients had a previous coronary stent implantation and no Valvular Calcification with Agatston Score > 50
  4. Chronic kidney disease (CKD) Stage V (GFR <15 mL)
  5. Liver disease with coagulopathy or other bleeding disorders including cirrhotic patients with Child Pugh B and C
  6. Acute gastrointestinal diseases
  7. Clinically significant active bleeding
  8. Alcohol, opioids or drug abuse
  9. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
  10. Patient is unwilling or unable to give informed consent
  11. Patient is unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
  12. Participation in a parallel interventional clinical trial
  13. Patient has been committed to an institution by legal or regulatory order
  14. Pregnant or lactating women
  15. Female patient capable of bearing children without highly effective methods of birth control
  16. 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
  17. Neuraxial Anaesthesia or spinal/epidural puncture
  18. Known Endocarditis
  19. Known Lactose intolerance
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02066662


Contacts
Contact: Vincent Brandenburg, Prof. Dr. med. 0049 241 80 ext 36072 vmbrandenburg@aol.com
Contact: Irina Viol, M.Sc. 0049 241 80 ext 37864 iviol@ukaachen.de

Locations
Germany
Hospital Coburg, Med. Clinic II for Internal Medicine and Cardiology Recruiting
Coburg, Bavaria, Germany, 96450
Contact: Johannes Brachmann, Prof.         
Contact: Steffen Schnupp, Dr.         
University Hospital Aachen, Department of Cardiology Recruiting
Aachen, North Rhine Westphalia, Germany, 52074
Contact: Vincent Brandenburg, Prof. Dr. med.    0049 241 80 ext 36072    vmbrandenburg@aol.com   
Principal Investigator: Vincent Brandenburg, Prof. Dr. med.         
Sub-Investigator: Nikolaus Marx, Prof. Dr. med.         
St.-Antonius-Hospital Eschweiler, Internal Medicine Recruiting
Eschweiler, North Rhine Westphalia, Germany, 52249
Contact: Uwe Janssens, Prof. Dr.    0049 2403 ext 761227    uwe.janssens@sah-eschweiler.de   
Principal Investigator: Uwe Janssens, Prof. Dr.         
Sub-Investigator: Andreas Niedeggen, Dr.         
Sponsors and Collaborators
RWTH Aachen University
Bayer
  More Information

Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT02066662     History of Changes
Other Study ID Numbers: 12-001
First Submitted: February 17, 2014
First Posted: February 19, 2014
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by RWTH Aachen University:
Coronary or Valvular Calcification
Agatston Score
Rivaroxaban
Coumarin
Oral Anticoagulation Therapy (OAT)
Atrial Fibrillation
Pulmonary Embolism

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Pulmonary Embolism
Calcinosis
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Rivaroxaban
Phenprocoumon
Vitamin K
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Antifibrinolytic Agents
Fibrin Modulating Agents
Hemostatics
Coagulants
Vitamins
Micronutrients


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