Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism
Brief Summary: The purpose of this study is to determine if tenecteplase plus enoxaparin is safe and effective in the treatment of patients with severe submassive pulmonary embolism.


Options:
A: Inclusion Criteria:

* Computed tomography (CT) evidence of proximal PE (filling defect in at least one main or segmental pulmonary artery)
* PE symptom duration less than or equal to (\<=)14 days
* Informed consent can be obtained from participant or Legally Authorized Representative (LAR)
* Massive PE (syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or
* Submassive PE (RV diameter-to-LV diameter greater than or equal to \[\>=\] 0.9 on contrast-enhanced chest CT)

Exclusion Criteria:

* Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year
* Recent (within one month) or active bleeding from a major organ
* Hematocrit less than (\<) 30 percent (%)
* Platelets \< 100 thousand/microliter (mcL)
* International Normalized Ratio (INR) greater than (\>) 3
* Activated partial thromboplastin time (aPTT) \>50 seconds on no anticoagulants
* Major surgery within seven days of screening for study enrollment
* Serum creatinine \>2 milligrams/deciliter (mg/dL)
* Clinician deems high-risk for catastrophic bleeding
* History of heparin-induced thrombocytopenia (HIT)
* Pregnancy
* Catheter-based pharmacomechanical treatment for pulmonary embolism within 3 days of study enrollment
* Systolic blood pressure less than 80 mm Hg despite vasopressor or inotropic support
* Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR)
* Evidence of irreversible neurological compromise
* Life expectancy \<30 days
* Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study
* Previous enrollment in the SEATTLE study
B: 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
C: Inclusion Criteria:

1. First episode of acute symptomatic PE that was objectively diagnosed\* within last 10 days
2. Treated with anticoagulants
3. ≥ 18 years old

   * PE will be diagnosed if there is a high probability V/Q scan (as per PIOPED Study criteria 66), an intraluminal filling defect in segmental or larger vessels on CTPA or a constant intraluminal filling defect or abrupt cut-off of vessels greater than 2.5 mm diameter on pulmonary angiography 8,10. Patients with non-definitive test results (e.g. low or intermediate probability V/Q scan, subsegmental PE on CTPA (\~5% of PE patients 12) will not be included in order to have a strictly defined population of patients with definite PE.

Exclusion Criteria:

1. Contraindication or unable to perform CPET or 6MWT (amputated or paralyzed limb(s), severe lower extremity arthritis, preexisting cardiopulmonary condition precluding exercise including unstable angina or myocardial infarction in last 6 weeks, uncontrolled hypertension, serious cardiac dysrhythmia on resting EKG \[severe bradycardia or tachycardia, sick sinus syndrome or multifocal premature ventricular contractions\] and syncope)
2. Contraindication to CTPA (allergy to iodinated contrast, CrCl or eGFR \< 30 ml/min)
3. Severe comorbidity (congestive heart failure \[LVEF \< 35%\], severe COPD or restrictive lung disease \[FEV1\<50%, chronic need for oxygen therapy\])
4. Previous DVT (as \~40% of patients with proximal DVT have asymptomatic PE on lung imaging 67)
5. Life expectancy \< 1 year (e.g. active or terminal cancer, end-stage cardiac or respiratory disease).
6. Pregnancy or lactation
7. Unable to read questionnaire in English or French
8. Unable to return to study centre for required follow-up visits
9. Unable or unwilling to provide written informed consent
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: B