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Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification

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ClinicalTrials.gov Identifier: NCT02066662
Recruitment Status : Active, not recruiting
First Posted : February 19, 2014
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
RWTH Aachen University

Tracking Information
First Submitted Date  ICMJE February 17, 2014
First Posted Date  ICMJE February 19, 2014
Last Update Posted Date August 21, 2019
Study Start Date  ICMJE July 2013
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 28, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
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 ]
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
Change History Complete list of historical versions of study NCT02066662 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • 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, 9 and 12 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 and 12 month FU ]
Current Other Pre-specified Outcome Measures
 (submitted: May 8, 2017)
  • 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 ]
Original Other Pre-specified Outcome Measures
 (submitted: February 17, 2014)
  • Occurrence of major cardiovascular complications (MACE) [ Time Frame: 1 week, 1, 6, 9, 12 month FU ]
  • Non- major bleedings [ Time Frame: 1week, 1, 6, 9, 12 month FU ]
  • Major bleedings [ Time Frame: 1 week, 6, 9, 12 month FU ]
 
Descriptive Information
Brief Title  ICMJE Rivaroxaban Compared to Vitamin K Antagonist Upon Development of Cardiovascular Calcification
Official Title  ICMJE 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)
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 optionally.

Primary outcome measures will be assessed after all active patients will have completed 12-months study visit (interim analysis)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • 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
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 22, 2018)
192
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2014)
348
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 in a way which makes coronary artery calcification scoring impossible or unreliable 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02066662
Other Study ID Numbers  ICMJE 12-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party RWTH Aachen University
Study Sponsor  ICMJE RWTH Aachen University
Collaborators  ICMJE Bayer
Investigators  ICMJE Not Provided
PRS Account RWTH Aachen University
Verification Date July 2019

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