Please select the eligibility criteria that correspond to the clinical trial below.
Title: Once-daily Oral Direct Factor Xa Inhibitor BAY59-7939 in Patients With Acute Symptomatic Deep-vein Thrombosis The Einstein-DVT Dose-finding Study. A Phase II Evaluation.
Brief Summary: The purpose of this study is to determine the optimal dose of BAY 59-7939 and to compare the safety and effectiveness of this new drug with the standard way of treatment of deep vein thrombosis (heparin infusion plus one of the vitamin K antagonists), taking into account new events of thrombosis and pulmonary embolism and bleeding risk.


Options:
A: 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
B: Inclusion Criteria:

* Confirmed acute symptomatic DVT, i.e. proximal or extensive calf-vein thrombosis involving at least the upper third part of the calf veins, without concomitant symptomatic PE
* Written informed consent

Exclusion Criteria:

* Legal lower age limitations (country specific)
* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT
* Other indication for VKA than PE/DVT
* More than 36 hours pre-randomization treatment with therapeutic dosages of (LMW) heparin or more than a single dose of VKA prior to randomization
* Participation in another pharmacotherapeutic study within the prior 30 days
* Creatinine clearance \< 30 mL/min, impaired liver function (transaminases \> 2 x ULN), or bacterial endocarditis
* Life expectancy \< 3 months
* Active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin
* Uncontrolled hypertension: systolic blood pressure \> 200 mmHg and diastolic blood pressure \> 110 mmHg
* Pregnancy or childbearing potential without proper contraceptive measures
* Any other contraindication listed in the labeling of warfarin, acenocoumarol, phenprocoumon, fluindione, UFH, enoxaparin, or tinzaparin
* Systemic treatment with azole compounds or other strong CYP3A4 inhibitors (e.g. ketoconazole, fluconazol, itraconazole, HIV protease inhibitors) within 4 days prior to randomization and during the study
C: Inclusion criteria Patients with non-valvular atrial fibrillation (AF), at moderate to high risk of stroke, or systemic embolism with at least one additional risk factor (i.e. previous ischemic stroke, TIA, or systemic embolism, left ventricular dysfunction, age \>=75 years, age \>=65 with either diabetes mellitus, history of coronary artery disease or hypertension)

Exclusion criteria

1. Prosthetic heart valves requiring anticoagulation per se, or hemodynamically relevant valve disease that is expected to require surgical intervention during the course of the study
2. Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days
3. Conditions associated with an increased risk of bleeding
4. Contraindication to warfarin treatment
5. Reversible causes of atrial fibrillation (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism).
6. Plan to perform a pulmonary vein ablation or surgery for cure of the AF
7. Severe renal impairment (estimated creatinine clearance \<=30 mL/min)
8. Active infective endocarditis
9. Active liver disease
10. Women who are pregnant, lactating, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study
11. Anaemia (haemoglobin \<100g/L) or thrombocytopenia (platelet count \<100 x 109/L)
12. Patients who have developed transaminase elevations upon exposure to ximelagatran
13. Patients who have received an investigational drug in the past 30 days or are participating in another drug study
14. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than the expected duration of the trial due to concomitant disease, or has any condition which in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse)
15. Any known hypersensitivity to galactose if the warfarin used contains galactose.
D: Inclusion criteria:

Inclusion_Criteria

* Acute symptomatic deep vein thrombosis (DVT)
* Pulmonary embolism (PE) 3-12 months prior to screening, which has been documented by objective testing

Exclusion criteria:

Exclusion_Criteria

* Symptomatic DVT or PE at screening Interruption of anticoagulant therapy for 2 or more weeks during the 3-12 months of treatment for the prior VTE.
* Patients who in the investigators judgement are perceived as having an excessive risk of bleeding Elevated Aspartate aminotransferase (AST) or Alanine tranminase (ALT) \> 2x ULN
* Severe renal impairment (estimated creatinine clearance \<= 30 ml/min)

Answer: B