Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: Purpose and rationale: Acute pulmonary embolism (PE) is a common and often fatal disease, with an approximately 30% mortality rate without treatment. Treatment is important to reduce mortality and recurrence in acute PE. Therapeutic options for PE include subcutaneous low molecular weight heparin (SC LMWH), intravenous unfractionated heparin (IV UFH), subcutaneous unfractionated heparin and subcutaneous fondaparinux with or without thrombolysis. In the treatment of acute PE, SC LMWH has been shown, at least, as effective and safe as IV UFH \[4\]. Compared to IV UFH, SC LMWH associated with lower mortality, fewer recurrent thrombotic events and less major bleeding. Current guidelines recommend use of SC LMWH for most hemodynamically stable patients with PE and they say that SC LMWH have not been tested in the setting of acute massive PE.

The purpose of this study is to demonstrate that SC LMWH is as safe as IV UFH in the treatment of acute PE in combination with thrombolytic treatment.


Options:
A: Inclusion Criteria:

* Confirmed diagnosis of acute proximal DVT based on contrast-enhanced Multi detector-row CT (MDCT) (not more than 10 days after the onset of the symptoms of DVT)
* Age:20 years
* Gender: No restriction
* Hospitalization status: Subjects who are able to stay at the hospital at least during the initial treatment period
* Written informed consent from the subject him/herself or his/her legally acceptable representative. Written informed consent from the subject's legally acceptable representative must be obtained if the subject is incapable of giving consent

Exclusion Criteria:

* Symptomatic PE
* Requirement for surgical thrombectomy, catheter intervention and thrombolytic therapy for the current DVT
* Subjects (for example, with free-floating thrombus in the femoral vein or ilium by MDCT at screening) for whom insertion of inferior vena cava filter is indicated or subjects in whom inferior vena cava filter is present
* Anticoagulant therapy for at least 24 hours to treat the current episode prior to entry into the study
* Active, clinically significant bleeding
* Thrombocytopenia (platelet count \<10×10⁴/µL at screening)
* Concurrent conditions with bleeding risk (e.g., ulcer of the gastrointestinal tract, diverticulitis of the gastrointestinal tract, colitis, acute bacterial endocarditis, severe hypertension, or severe diabetes) or bleeding tendency
* Severe hepatic disorder
* Known hypersensitivity to heparin, low-molecular-weight heparin (LMWH) or warfarin
* Previous history of cerebral hemorrhage
* Brain, spinal, or ophthalmological surgery within 3 months prior to entry into this study
* Previous history of Heparin-induced thrombocytopenia
* Patients for whom anticoagulant therapy is contraindicated or who cannot be taken off anticoagulant therapy due to coexistent condition (e.g. prosthetic heart valve implant)
* Severe renal disorder (serum creatinine \>2.0 mg/dL \[180 µmol/L\] at screening) in a well hydrated subject
* QT interval prolonged (QT interval corrected by Bazett's formula \[QTcB\] ≥450 msec; for patients with bundle branch block QTcB ≥480 msec) at screening
* Documented hypersensitivity to contrast media
* Use of any contraindicated drug that cannot be combined with the injection of contrast medium \[e.g., antihyperglycemics, such as biguanides (metformin hydrochloride, buformin hydrochloride)\]
* Participation in any other therapeutic drug study or a clinical study within 6 months prior to entry into this study
* Previous participation in a study of GSK576428 \[Fondaparinux Sodium; including the studies of Org31540/SR90107A (ex-project code)\] or previous exposure to the therapeutic dose of GSK576428
* Drug or alcohol abuse
* Systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg
* Recent surgery within 3 days prior to entry into the study
* Life expectancy \<3 months
* Pregnant women, nursing mothers, women who may be pregnant, or women contemplating pregnancy during the study period
* Others whom the investigator or subinvestigator considers not eligible for the study
B: Inclusion Criteria:

* Subjects with a confirmed diagnosis (by Multi detector-row CT \[MDCT\]) of acute symptomatic PE who are hemodynamically stable (i.e., the condition where anticoagulant therapy alone are indicated) (the time from onset should be no longer than 5 days, and subjects with or without symptomatic DVT are eligible)
* Age: \>=20 years
* Gender: No restriction Female subjects must either be of non-childbearing potential (post-menopausal \>1 year, hysterectomy, or sterilization), or of childbearing potential, has a negative pregnancy test at screening, and agree to use contraception throughout the study period.
* Hospitalization status: Subjects who are able to stay at the hospital at least during the initial treatment period.
* Written informed consent from the subject him/herself or his/her legally acceptable representative. Written informed consent from the subject's legally acceptable representative must be obtained if the subject is incapable of giving consent.

Exclusion Criteria:

* Shock or hemodynamic instability\*.

  \*: Defined as shock or decreased blood pressure (systolic blood pressure \<90 mmHg or \>=40 mmHg) lasting for at least 15 minutes and does not represent hemodynamically unstable conditions due to newly emergent arrhythmia, dehydration or sepsis.
* Right cardiac function failure detected by echocardiography at screening.
* Requirement for surgical thrombectomy, catheter intervention and thrombolytic therapy for the current PE.
* Subjects (for example, with free-floating thrombus in the femoral vein or ilium by MDCT at screening) for whom insertion of inferior vena cava filter is indicated or subjects in whom inferior vena cava filter is present.
* Prior to entry into the study, therapeutic dosage of anticoagulants for more than 24 hours to treat the current episode.
* Active, clinically significant bleeding
* Thrombocytopenia (platelet count \<10×10⁴/µL at screening)
* Concurrent conditions with bleeding risk (e.g., ulcer of the gastrointestinal tract, diverticulitis of the gastrointestinal tract, colitis, acute bacterial endocarditis, severe hypertension\*, or severe diabetes) or bleeding tendency.

  \*: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg
* Severe hepatic disorder
* Known hypersensitivity to heparin, low-molecular-weight heparin (LMWH) or warfarin
* Previous history of cerebral hemorrhage
* Brain, spinal, or ophthalmological surgery within 3 months prior to entry into this study
* Previous history of Heparin-induced thrombocytopenia
* Patients for whom anticoagulant therapy is contraindicated or who cannot be taken off anticoagulant therapy due to coexistent condition (e.g. prosthetic heart valve implant).
* Severe renal disorder (serum creatinine \>2.0 mg/dL \[180 µmol/L\] at screening) in a well hydrated subject
* Documented hypersensitivity to contrast media
* Use of any contraindicated drug that cannot be combined with the injection of contrast medium \[e.g., antihyperglycemic metformin hydrochloride (Glycoran®, Melbin®)\]
* Participation in any other therapeutic drug study or a clinical study within 6 months prior to entry into this study
* Previous participation in a study of GSK576428
* Drug or alcohol abuse
* Systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg
* Recent surgery within 3 days prior to entry into the study
* Life expectancy \<3 months
* Pregnant women, nursing mothers, women who may be pregnant, or women contemplating pregnancy during the study period
* Others whom the investigator or subinvestigator considers not eligible for the study
C: Inclusion Criteria:

* Adults, age ≥ 18 years
* Patients who have signed the study informed consent form prior to initiation of any study-related procedure.
* Acute massive PE patients who require thrombolytic treatment.

Exclusion Criteria:

* Patients who have a contraindication to use of anticoagulation and thrombolysis, such as active bleeding, stroke, cranial trauma, or neurologic surgery within the preceding 6 months, current pregnancy, major surgery, or biopsy within the preceding 7 days, major trauma within the preceding 10 days, gastrointestinal bleeding within the preceding 1 months during their admission.
* Patients who received any anticoagulation medication prior to admission to the hospital.
D: Inclusion Criteria:

* A diagnosis of acute venous thromboembolism (VTE,DVT and /or PE)

Exclusion Criteria:

* Contraindication to subcutaneous (sc) route of administration (eg:shock (evidence of poor peripheral perfusion), major surgery within 48 hours)
* Active Bleeding process
* Comorbid condition limiting expected survival to less than 3 months
* Current treatment with therapeutic dose of UFH, LMWH, danaparoid sodium, or a direct thrombin inhibitor for more than 48 hours
* Currently on long term warfarin or heparin therapy
* Allergy to heparin or history of heparin induced thrombocytopenia
* Currently pregnant
* Contraindication to contrast media (eg: allergy or creatinine \>200 umol/L).
* Currently enrolled or will be enrolled in a competing study
* Geographically inaccessible for follow-up assessment

Answer: C