Please select the eligibility criteria that correspond to the clinical trial below.
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)
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.


Options:
A: Inclusion Criteria:

* Age \> 18 years
* Social security affiliation
* Written informed consent
* Solid active cancer, high grade lymphoma or myeloma treated with Immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide). Active cancer is defined as the presence of measurable disease or ongoing (or planned) chemotherapy, radiotherapy or targeted therapy at inclusion.
* Histologically or cytologically proven cancer.
* Symptomatic venous thromboembolism objectively confirmed diagnosed because of symptoms or discovered incidentally
* High-risk of recurrent Venous thromboembolism (VTE) defined by a score of 0 or ≥ 1, using the following criteria: female sex (+1), lung cancer (+1), breast cancer (-1) non metastatic tumor (-2), previous VTE (+1).

Exclusion Criteria:

* Exclusive adjuvant hormonal treatment with no measurable residual disease
* Sub-segmental isolated pulmonary embolism (PE) without associated proximal DVT
* Isolated distal deep vein thrombosis (DVT) of the legs
* Isolated upper-extremity DVT or superior vena cava thrombosis
* Isolated visceral thrombosis
* Platelet count \< 50 000 G/L
* Active bleeding
* Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C
* Hemostatic defect with contraindication to anticoagulant treatment at therapeutic dosage
* Vena cava filter at inclusion
* Fibrinolytic therapy within 3 days preceding inclusion
* Creatinine clearance \< 30 ml/min according to Cockcroft-Gault formula
* Previous heparin-induced thrombocytopenia
* Anticoagulant treatment at curative dosage for more than 3 days before inclusion
* Pregnancy or lack of effective contraceptive treatment for women of childbearing age
* Treatment with both strong CYP3A4 and P-glycoprotein (PgP) inhibitors: protease inhibitors for HIV disease, systemic ketoconazole
* Treatment with a strong CYP3A4 inducer: rifampicin, carbamazepine, phenytoin.
* Life expectancy \< 3 months
* Eastern Cooperative Oncology Group (ECOG) level 3 or 4
B: Inclusion Criteria:

* Confirmed acute lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis
* Active cancer defined as metastatic disease and/or any evidence of cancer on cross-sectional or positron emission tomography (PET) imaging, cancer related surgery, chemotherapy or radiation therapy within the past 6 months; note: non-melanoma skin cancer does not meet the cancer requirement
* Life expectancy \>= 60 days
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
* Obtained =\< 30 days prior to randomization: Platelet count \>= 50,000/mm\^3
* Obtained =\< 30 days prior to randomization: Alanine aminotransferase (ALT) or aspartate transaminase (AST) =\< 3 x upper limit of normal (ULN)
* Obtained =\< 30 days prior to randomization: International normalized ratio (INR) =\< 1.6 (if not taking anticoagulant therapy)
* Obtained =\< 30 days prior to randomization: Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft-Gault formula
* Negative serum or urine pregnancy test done =\< 24 hours prior to randomization, for women of childbearing potential only; note: a women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes
* Ability to complete questionnaire(s) by themselves or with assistance
* Ability to provide informed written consent
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

* Any of the following:

  * Pregnant women
  * Nursing women
  * Men or women of childbearing potential who are unwilling to employ adequate contraception

    * Note: women of child bearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 33 days after finishing the last dose
    * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 93 days after finishing the last dose
    * Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however they must still undergo pregnancy testing as described in this section
* Note: investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception; highly effective methods of contraception have a failure rate of \< 1% when used consistently and correctly
* At a minimum, subjects must agree to the use of one method of highly effective contraception as listed below:

  * HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

    * Male condoms with spermicide
    * Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject?s WOCBP partner
    * Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug
    * IUDs, such as ParaGard
    * Tubal ligation
    * Vasectomy
    * Complete abstinence

      * Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence
* Treatment with an anticoagulant for more than 7 days for the current blood clot, prior to randomization
* Active bleeding
* Severe hypersensitivity reaction to apixaban, dalteparin, heparin or pork products (e.g., anaphylactic reactions)
* Use of the following CYP3A4 inducers: rifampin, rifabutin, carbamazepine, efavirenz, phenobarbital, phenytoin, fosphenytoin, primidone, and St. John?s wort)
* Thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) that will be continued on study
* Severe liver disease (known cirrhosis Childs Pugh class B or C), or active hepatitis
* Use of a Factor Xa inhibitor (e.g. apixaban, rivaroxaban, or edoxaban) =\< 3 months prior to randomization
* Treatment of a thromboembolic event =\< 6 months prior to randomization
* Documented venous thromboembolism while on therapeutic anticoagulation (?anticoagulation failure?)
* Mechanical heart valve
* Documented hemorrhagic tendencies
* Bacterial endocarditis
* History of heparin induced thrombocytopenia
* Any of the following conditions:

  * Intracranial bleeding =\< 6 months prior to randomization
  * Intraocular bleeding =\< 6 months prior to randomization
  * Gastrointestinal bleeding and/or endoscopically proven ulcer =\< 6 months prior to randomization
  * Head trauma or major trauma =\<1 month prior to randomization
  * Neurosurgery =\< 2 weeks prior to randomization
  * Major surgery =\< 1 week prior to randomization
  * Overt major bleeding at the time of randomization
  * Gross hematuria at the time of randomization
C: Inclusion Criteria:

* Male or female subjects with age ≥ 18 years or the otherwise legal lower age according to the country of residence;
* Confirmed acute lower extremity proximal DVT or PE for which long term treatment with low molecular weight heparin (LMWH) is indicated;
* Cancer, other than basal-cell or squamous-cell carcinoma of the skin;
* Able to provide written informed consent.

Exclusion Criteria:

* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) episode of DVT and/or PE;
* Treatment with therapeutic doses of an anticoagulant other than that used for pretreatment of the current (index) VTE episode prior to randomization;
* Active bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban;
* Any other contraindication listed in the local labeling of dalteparin, enoxaparin, or edoxaban;
D: 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

Answer: D