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

February 17, 2014
September 24, 2014
July 2013
January 2016   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT02066662 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
  • 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 ]
Same as current
 
Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification
Influence of Rivaroxaban Compared to Vitamin K Antagonist Treatment Upon Development of Cardiovascular Calcification in Patients With Atrial Fibrillation and/ or Pulmonary Embolism

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • 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

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
  • 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
    Intervention: Drug: Rivaroxaban or 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.
    Intervention: Drug: Rivaroxaban or Marcumar
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
253
January 2016
January 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
Germany
 
NCT02066662
12-001
No
RWTH Aachen University
RWTH Aachen University
Bayer
Not Provided
RWTH Aachen University
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP