Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Multicenter, Randomized, Double Blind Study Comparing the Efficacy and Safety of Single Bolus i.v. Tenecteplase Versus Placebo in Normotensive Patients With Pulmonary Embolism and Right Ventricular Dysfunction
Brief Summary: To assess the efficacy and safety of Tenecteplase versus Placebo in normotensive patients with sub-massive Pulmonary Embolism and Right Ventricular Dysfunction (RVD) all receiving unfractionated heparin (UFH)


Options:
A: Inclusion Criteria:

* Pulmonary vascular imaging positive for PE within the previous 24 hours
* Ability to provide written informed consent and comply with study assessments for the full duration of the study
* Age \>17 years
* Evidence of severe PE: RV hypokinesis on echocardiography, abnormal troponin I or T (any non-normal including indeterminate values, using local reference thresholds) or BNP measurement \>90 pg/mL or NT proBNP \>900 pg/ml (not more than 6 hours prior to CT angiography and not more than 30 hours before enrollment) or a pulse oximetry reading \<95% within previous two hours (\<93% in Denver).

Exclusion Criteria:

* Systolic blood pressure \< 90 mm Hg at time of informed consent
* Do not resuscitate or do not intubate order
* Systemic fibrinolytic treatment within previous 7 days
* Inability to follow-up at 3 months
* Documented gastrointestinal bleeding within previous 30 days
* Active hemorrhage in any of the following sites at the time of enrollment: intraperitoneal, retroperitoneal, pulmonary, uterine, bladder, or nose.
* Head trauma causing loss of consciousness within previous 7 days
* Any history of hemorrhagic stroke
* Ischemic stroke within the past year
* Prior history of heparin-induced thrombocytopenia
* History of intraocular hemorrhage
* Intracranial metastasis
* Known inherited bleeding disorder, e.g., hemophilia
* Platelet count \< 50,000/uL
* Prothrombin time with an INR \>1.7
* Chest, abdominal, intracranial or spinal surgery within the previous 14 days
* Subacute bacterial endocarditis
* Pregnancy (positive pregnancy test)
* Prior enrollment in the study
* Current treatment with fondiparinux, dalteparin, a direct thrombin inhibitor or administration of a glycoprotein inhibitor within the previous 48 hours.
* Known pericarditis
* Allergy to heparins,or tenecteplase
* Elapsed time that would preclude drug or placebo administration within 24 hours after diagnosis
* Evidence of non-end stage kidney injury (creatinine clearance \< 30 ml/min without chronic hemodialysis treatment; chronic hemodialysis-treated patients are eligible)
* Preexisting end-stage cardiopulmonary disease (heart failure with left ventricular ejection fraction \<20%, known severe pulmonary hypertension or other lung disease causing permanent dependence upon oxygen)
* Any other condition that the investigator believes would pose a significant hazard to the subject
B: Inclusion Criteria:

* PTE confirmed either by a high probability ventilation-perfusion lung scanning (V/Q scan) or by CTPA.
* massive PTE patients with haemodynamic instability and/or cardiogenic shock
* Anatomic obstruction more than 2 lobes on CTPA and/or defect more than 7 segments on V/Q scan with evidence of right ventricular dysfunction (RVD) and pulmonary hypertension on echocardiography
* Symptoms within 15 days
* Written informed consent was obtained from all the patients before randomization

Exclusion Criteria:

* Received parenteral heparin for more than 72 hours
* Known allergic to urokinase
* Thrombolytic contraindications such as:

  1. active bleeding or spontaneous intracranial hemorrhage;
  2. major surgery, organ biopsy or recent puncture of a non-compressible vessel less than 10 days;
  3. cerebral arterial thrombosis within 2 months;
  4. gastro-intestinal bleeding within 10 days;
  5. major trauma within the past 15 days;
  6. neurosurgery or ophthalmologic operation with 30 days;
  7. uncontrolled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 110 mmHg);
  8. recent external cardiac resuscitation manoeuvres;
  9. platelet count \< 100 000/mm3 at admission;
  10. pregnancy, puerperium or lactation with 2 weeks;
  11. infectious pericarditis or endocarditis;
  12. severe hepatic and kidney dysfunction;
  13. hemorrhagic retinopathy due to diabetes;
  14. a known bleeding disorder.
C: Inclusion Criteria:

* age between 18 and 85;
* symptomatic PE confirmed by: high probability lung scan, or intermediate probability lung scan and objectively confirmed deep vein thrombosis, or spiral CT-scan or pulmonary angiography or TE echocardiography;
* normal blood pressure (SBP \>100mmHg);
* RVD at echocardiography (see criteria);
* written informed consent.

Exclusion Criteria:

* absence of RVD at echocardiography;
* shock or hypotension (SBP \< 100 mmHg);
* therapeutic heparin (UFH or LMWH) treatment for more than 48 hours prior to randomization;
* administration of thrombolytic agents within the previous 4 days;
* vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
* chronic pulmonary hypertension or severe COPD;
* hypertension defined as blood pressure \>180/110 mm Hg (systolic BP \>180 mm Hg and/or diastolic BP \>110 mm Hg) on a single, reliable measurement during current admission at enrolling site prior to randomisation;
* use of GP IIb/IIIa antagonists within the preceding 7 days;
* significant bleeding disorders either at present or within the past 6 months;
* active peptic ulceration;
* known diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions;
* known haemorrhagic diathesis;
* known arterial aneurysm and known arterial/venous malformation;
* known neoplasm with increased bleeding risk;
* prolonged cardiopulmonary resuscitation (\>10 minutes) in the previous two weeks;
* current oral anticoagulation;
* major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months;
* any known history of stroke or transient ischaemic attack (TIA) or dementia;
* any recent head trauma and any other trauma occurring after onset of the current pulmonary embolism;
* any known history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery);
* known subacute bacterial endocarditis;
* known acute pancreatitis;
* known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension
* (oesophageal varices) and active hepatitis;
* pregnancy or lactation or parturition within the previous 30 days;
* women of childbearing potential must have a negative pregnancy test, or use a medically accepted method of birth control;
* treatment with an investigational drug under another study protocol in the past 7 days;
* previous enrolment in this study;
* known hypersensitivity to Tenecteplase, Alteplase, unfractionated heparin, or to any of the excipients;
* anticipated or obvious problem with vascular access;
* any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated;
* inability to follow protocol requirements
D: Inclusion Criteria:

* Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein.

Exclusion Criteria:

* Age less than 16 years or greater than 75 years.
* Symptom duration \> 14 days for the DVT episode in the index leg (i.e., non-acute DVT).
* In the index leg: established PTS, or previous symptomatic DVT within the last 2 years.
* In the contralateral (non-index) leg: symptomatic acute DVT a) involving the iliac and/or common femoral vein; or b) for which thrombolysis is planned as part of the initial therapy.
* Limb-threatening circulatory compromise.
* Pulmonary embolism with hemodynamic compromise (i.e., hypotension).
* Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.
* Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
* Hemoglobin \< 9.0 mg/dl, INR \> 1.6 before warfarin was started, or platelets \< 100,000/ml.
* Moderate renal impairment in diabetic patients (estimated glomerular filtration rate \[GFR\] \< 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR \< 30 ml/min).
* Active bleeding, recent (\< 3 mo) GI bleeding, severe liver dysfunction, bleeding diathesis.
* Recent (\< 3 mo) internal eye surgery or hemorrhagic retinopathy; recent (\< 10 days) major surgery, cataract surgery, trauma, cardiopulmonary resuscitation, obstetrical delivery, or other invasive procedure.
* History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
* Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: patients with non-melanoma primary skin cancers are eligible to participate in the study.
* Severe hypertension on repeated readings (systolic \> 180 mmHg or diastolic \> 105 mmHg).
* Pregnant (positive pregnancy test, women of childbearing potential must be tested).
* Recently (\< 1 mo) had thrombolysis or is participating in another investigational drug study.
* Use of a thienopyridine antiplatelet drug (except clopidogrel) in the last 5 days.
* Life expectancy \< 2 years or chronic non-ambulatory status.
* Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Answer: C