Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3b, Prospective, Randomized, Open-label, Blind Evaluator (PROBE) Study Evaluating the Efficacy and Safety of (LMW) Heparin/Edoxaban Versus Dalteparin in Venous Thromboembolism Associated With Cancer
Brief Summary: The primary objective is to demonstrate the non-inferiority of edoxaban (preceded by a short course of LMWH) compared with dalteparin for the prevention of the combined outcome of recurrent venous thromboembolism (VTE) or major bleeding in subjects with VTE associated with cancer during a 12-month study period. If non-inferiority is established, LMWH/edoxaban will be compared with dalteparin for superiority.


Options:
A: Inclusion Criteria:

Patients \> 18 years and weighing more than 40 kg who are scheduled for primary elective total knee arthroplasty according to the 'joint care program' and want to provided signed informed consent are eligible for the study.

Exclusion Criteria:

* a known inherited or acquired clinically significant active high risk of bleeding or bleeding disorder;
* major surgery, trauma, uncontrolled severe arterial hypertension, or myocardial infarction within the last 3 months;
* history of acute intracranial disease or hemorrhagic stroke;
* gastrointestinal or urogenital bleeding or ulcer disease within the last 6 months;
* cirrhotic patients with moderate hepatic impairment (aspartate or alanine aminotransferase (AST, ALT) levels higher than 2x the upper limit of the normal range (ULN) within the last month);
* severe renal insufficiency (creatinine clearance \< 30 mL/min);
* treatment with anticoagulants during study drug treatment;
* active malignant disease;
* pregnancy or breastfeeding;
* and unable to give informed consent.
B: Inclusion Criteria:

* Consecutive patients with a newly diagnosed, objectively confirmed: symptomatic or unsuspected, proximal lower-limb DVT or symptomatic PE or unsuspected PE in a segmental or more proximal pulmonary artery;
* Any type of cancer (other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor or intracerebral metastasis and acute leukemia);
* Signed and dated informed consent of the patient, available before the start of any specific trial procedure.

Exclusion Criteria:

* age \<18 years;
* ECOG Performance Status III or IV;
* life expectancy of less than 6 months;

Related to anticoagulant treatment:

* administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization;
* 3 or more doses of a vitamin K antagonist before randomization;
* thrombectomy, vena cava filter insertion, or thrombolysis used to manage the index episode;
* indication for anticoagulant treatment for a disease other than the index VTE episode;

Related to bleeding risk:

* thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;
* active bleeding or a high risk of bleeding contraindicating anticoagulant treatment;
* recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery
* hemoglobin level lower than 8 g/dL (5.0 mmol/L) or platelet count \<75x10\^9/L or history of heparin induced thrombocytopenia;
* creatinine clearance \< 30 ml /min based on the Cockcroft Gault equation;
* acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range;
* uncontrolled hypertension (systolic BP\> 180 mmHg or diastolic BP \> 100 mmHg despite antihypertensive treatment);
* concomitant use of strong inhibitors or inducers of both cytochrome P-450 3A4 and P-Glycoprotein;

Standard criteria:

* bacterial endocarditis;
* hypersensitivity to the active substance or to any of the excipients of study drug;
* patients participation in other pharmaco therapeutic program with an experimental therapy that is known to effect the coagulation system;
* childbearing potential without proper contraceptive measures, pregnancy, or breast feeding;
* any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study.
C: Inclusion criteria:

1. Patients with confirmed symptomatic PE or proximal DVT of the leg(s) who have been treated for 6 to 18 months with therapeutic dosages (intended INR between 2-3) of an oral VKA (e.g. warfarin, acenocoumarol, phenprocoumon, or fluindione) or RE-COVER study medication up to the moment of screening for the current study.
2. Written informed consent

Exclusion criteria:

1. Younger then 18 years of age
2. Indication for VKA other than DVT and/or PE
3. Patients in whom anticoagulant treatment for their index PE or DVT should be continued
4. Active liver disease or liver disease decreasing survival (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT \> 3 x ULN
5. Creatinine clearance \< 30 ml/min
6. Acute bacterial endocarditis
7. Active bleeding or high risk for bleeding.
8. Uncontrolled hypertension (investigators judgement)
9. Intake of another experimental drug within the 30 days prior to randomization into the study
10. Life expectancy \<6 months
11. Childbearing potential without proper contraceptive measures\*, pregnancy or breast feeding
D: 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;

Answer: D