Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by RWTH Aachen University
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT02066662
First received: February 17, 2014
Last updated: September 24, 2014
Last verified: September 2014
  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
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

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 Score) [ Time Frame: Cardiac Computertomography (CT) will be performed at screening, after 12 months and optional at 24 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD) [ Time Frame: Baseline, 6, 9 and 12 month FU ] [ Designated as safety issue: No ]
  • Progression of aortic calcification (aortic Agatston Score) [ Time Frame: screening and 12 month FU ] [ Designated as safety issue: No ]
  • Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging) [ Time Frame: baseline, 6, 9 and 12 month FU ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Occurrence of major cardiovascular complications (MACE) [ Time Frame: 1 week, 1, 6, 9, 12 month FU ] [ Designated as safety issue: Yes ]
  • Non- major bleedings [ Time Frame: 1week, 1, 6, 9, 12 month FU ] [ Designated as safety issue: Yes ]
  • Major bleedings [ Time Frame: 1 week, 6, 9, 12 month FU ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 253
Study Start Date: July 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (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 single 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02066662

Contacts
Contact: Vincent Brandenburg, Prof. Dr. med. 0049 241 80 ext 36072 vmbrandenburg@aol.com
Contact: Sigrid Gloeggler, M.Sc. 0049 241 80 ext 80202 sgloeggler@ukaachen.de

Locations
Germany
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   
Contact: Sigrid Gloeggler, M.Sc.    0049 241 80 ext 80202    sgloeggler@ukaachen.de   
Principal Investigator: Vincent Brandenburg, Prof. Dr. med.         
Sub-Investigator: Nikolaus Marx, Prof. Dr. med.         
Sponsors and Collaborators
RWTH Aachen University
Bayer
  More Information

No publications provided

Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT02066662     History of Changes
Other Study ID Numbers: 12-001
Study First Received: February 17, 2014
Last Updated: September 24, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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
Calcinosis
Embolism
Pulmonary Embolism
Arrhythmias, Cardiac
Calcium Metabolism Disorders
Cardiovascular Diseases
Embolism and Thrombosis
Heart Diseases
Lung Diseases
Metabolic Diseases
Pathologic Processes
Respiratory Tract Diseases
Vascular Diseases
Phenprocoumon
Rivaroxaban
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014