Clinical trial NCT02066662: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: 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
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2014-02-19
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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)

Eligibility 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 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

Primary outcomes:
measure: Progression of coronary and aortic valve calcification (Agatston, volume & mass score as assessed by cardiac CT)
timeFrame: Cardiac Computertomography (CT) will be performed at screening, after 12 months and at 24 months
Secondary outcomes:
measure: Serum chemistry including Matrix Gla Protein (MPG) level changes and Fetuin-A (baseline/ follow up)
timeFrame: baseline and 12 month Follow Up
measure: Changes in intima-media thickness of carotid artery (IMT) and flow-mediated vasodilation of brachial artery (FMD)
timeFrame: Baseline, 6, 12 and 24 month FU
measure: Progression of aortic calcification (aortic Agatston Score)
timeFrame: screening and 12 month FU
measure: Changes in ventricular diastolic function parameters as determined by echocardiography (strain/strain-rate imaging)
timeFrame: baseline, 6, 9, 12 and 24 month FU
Other outcomes:
measure: Occurrence of major cardiovascular complications (MACE)
timeFrame: 1 week, 1, 6, 9, 12 and 24 month FU
measure: Non- major bleedings
timeFrame: 1week, 1, 6, 9, 12 and 24 month FU
measure: Major bleedings
timeFrame: 1 week, 6, 9, 12 and 24 month FU
Locations:
city: Coburg
country: Germany
facility: Hospital Coburg, Med. Clinic II for Internal Medicine and Cardiology
state: Bavaria
city: Aachen
country: Germany
facility: University Hospital Aachen, Department of Cardiology
state: North Rhine Westphalia
city: Eschweiler
country: Germany
facility: St.-Antonius-Hospital Eschweiler, Internal Medicine
state: North Rhine Westphalia
Study officials:
References: