Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison Trial Evaluating Efficacy and Safety of Single i.v. Bolus Tenecteplase Plus Standard Anticoagulation as Compared With Standard Anticoagulation in Normotensive Patients
Brief Summary: Heparin is the reference therapy for most patients with pulmonary embolism. Some patients with sub-massive pulmonary embolism defined by normal blood pressure and dysfunction of the right ventricle have a higher mortality risk. It has been suggested that thrombolytic treatment, a drug that dissolves blood clots more rapidly, may reduce the mortality in those patients. The studies reported to date were unable to confirm or refute this hypothesis because the number of patients included in those studies is too low. The aim of the study is to compare thrombolytic treatment with heparin (which is the reference therapy for pulmonary embolism) in a large group of patients with sub-massive pulmonary embolism.


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 75
* symptomatic PE confirmed by: a high probability ventilation-perfusion lung scanning (V/Q scan) or the presence of intraluminal filling defect on spiral computed tomographic pulmonary angiography (CTPA)
* PTE patients with haemodynamic instability, or cardiogenic shock
* anatomic obstruction more than 2 lobes on CTPA, or defect more than 7 segments on V/Q scan combined with evidence of right ventricular dysfunction(RVD) and pulmonary hypertension on echocardiography
* written informed consent

Exclusion Criteria:

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

* Age 18 years or older
* Acute PE (first symptoms occurring 15 days or less before randomisation) confirmed by lung scan, or a positive spiral computed tomogram, or a positive pulmonary angiogram
* Right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test

Exclusion criteria:

* Haemodynamic collapse at presentation as defined above
* Known significant bleeding risk
* Administration of thrombolytic agents within the previous 4 days
* Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
* Uncontrolled hypertension defined as systolic BP \>180 mm Hg and/or diastolic BP \>110 mm Hg at randomisation
* Treatment with an investigational drug under another study protocol in the previous 7 days or greater, according to local requirements
* Previous enrolment in this study
* Known hypersensitivity to tenecteplase, alteplase, unfractionated heparin, or to any of the excipients
* Pregnancy, lactation or parturition within the previous 30 days. Women of childbearing age must have a negative pregnancy test or use a medically accepted method of birth control
* Known coagulation disorder (including vitamin K antagonists)
* Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated

Answer: D