1. anticipated transfer to another hospital (which is not a study site) within 72 hours 2. allergy or contraindications to tnk 3. contraindications to systemic anticoagulation 4. active bleeding 5. known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. 6. major gi or gu bleed within the past 3 weeks 7. history of hemorrhagic stroke 8. history of acute ischemic stroke in the last 90 days 9. high-risk (massive) acute pe (pe associated with hypotension (systolic bp \< 90 mmhg for \> 15 min). 10. pe associated with syncope and any degree of head trauma 11. pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. 12. administration of thrombolytic agent within the previous 7 days 13. pulmonary thrombectomy within the previous 30 days 14. uncontrolled hypertension defined as systolic blood pressure \>180 mm hg and/or diastolic blood pressure \>110 mm hg at randomization 15. severe ards (p/f ratio \< 100) 16. platelet count lower than 80,000/mm3 17. known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr \>1.7 18. arterial puncture at a non-compressible site within the past 5 days 19. prior brain surgery 20. severe trauma in the prior 2 weeks 21. major surgery in the prior 2 weeks 22. brain malignancy / metastases, brain tumor in past 5 years 23. brain avm or ruptured aneurysm at any time 24. acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization 25. cardiac tamponade 26. lumbar puncture with in past 7 days 27. known abdominal or thoracic aneurysm 28. acute or chronic renal failure requiring dialysis 29. chronic liver failure (acutely elevated liver function tests not an exclusion criterion) 30. bacterial endocarditis at time of study entry 31. seizure during pre-hospital course or during hospitalization for covid-19 32. currently on ecmo 33. pregnancy, lactation or parturition within the previous 30 days 34. patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. 35. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated 36. previous enrollment in this study

1. anticipated transfer to another hospital (which is not a study site) within 72 hours 2. allergy or contraindications to tnk 3. contraindications to systemic anticoagulation 4. active bleeding 5. known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. 6. major gi or gu bleed within the past 3 weeks 7. history of hemorrhagic stroke 8. history of acute ischemic stroke in the last 90 days 9. high-risk (massive) acute pe (pe associated with hypotension (systolic bp \< 90 mmhg for \> 15 min). 10. pe associated with syncope and any degree of head trauma 11. pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. 12. administration of thrombolytic agent within the previous 7 days 13. pulmonary thrombectomy within the previous 30 days 14. uncontrolled hypertension defined as systolic blood pressure \>180 mm hg and/or diastolic blood pressure \>110 mm hg at randomization 15. severe ards (p/f ratio \< 100) 16. platelet count lower than 80,000/mm3 17. known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr \>1.7 18. arterial puncture at a non-compressible site within the past 5 days 19. prior brain surgery 20. severe trauma in the prior 2 weeks 21. major surgery in the prior 2 weeks 22. brain malignancy / metastases, brain tumor in past 5 years 23. brain avm or ruptured aneurysm at any time 24. acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization 25. cardiac tamponade 26. lumbar puncture with in past 7 days 27. known abdominal or thoracic aneurysm 28. acute or chronic renal failure requiring dialysis 29. chronic liver failure (acutely elevated liver function tests not an exclusion criterion) 30. bacterial endocarditis at time of study entry 31. seizure during pre-hospital course or during hospitalization for covid-19 32. currently on ecmo 33. pregnancy, lactation or parturition within the previous 30 days 34. patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. 35. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated 36. previous enrollment in this study

anticipated transfer to another hospital (which is not a study site) within 72 hours allergy or contraindications to tnk contraindications to systemic anticoagulation active bleeding known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. major gi or gu bleed within the past 3 weeks history of hemorrhagic stroke history of acute ischemic stroke in the last 90 days high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). pe associated with syncope and any degree of head trauma pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. administration of thrombolytic agent within the previous 7 days pulmonary thrombectomy within the previous 30 days uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization severe ards (p/f ratio < 100) platelet count lower than 80,000/mm3 known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 arterial puncture at a non-compressible site within the past 5 days prior brain surgery severe trauma in the prior 2 weeks major surgery in the prior 2 weeks brain malignancy / metastases, brain tumor in past 5 years brain avm or ruptured aneurysm at any time acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization cardiac tamponade lumbar puncture with in past 7 days known abdominal or thoracic aneurysm acute or chronic renal failure requiring dialysis chronic liver failure (acutely elevated liver function tests not an exclusion criterion) bacterial endocarditis at time of study entry seizure during pre-hospital course or during hospitalization for covid-19 currently on ecmo pregnancy, lactation or parturition within the previous 30 days patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated previous enrollment in this study

anticipated transfer to another hospital (which is not a study site) within 72 hours allergy or contraindications to tnk contraindications to systemic anticoagulation active bleeding known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. major gi or gu bleed within the past 3 weeks history of hemorrhagic stroke history of acute ischemic stroke in the last 90 days high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). pe associated with syncope and any degree of head trauma pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. administration of thrombolytic agent within the previous 7 days pulmonary thrombectomy within the previous 30 days uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization severe ards (p/f ratio < 100) platelet count lower than 80,000/mm3 known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 arterial puncture at a non-compressible site within the past 5 days prior brain surgery severe trauma in the prior 2 weeks major surgery in the prior 2 weeks brain malignancy / metastases, brain tumor in past 5 years brain avm or ruptured aneurysm at any time acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization cardiac tamponade lumbar puncture with in past 7 days known abdominal or thoracic aneurysm acute or chronic renal failure requiring dialysis chronic liver failure (acutely elevated liver function tests not an exclusion criterion) bacterial endocarditis at time of study entry seizure during pre-hospital course or during hospitalization for covid-19 currently on ecmo pregnancy, lactation or parturition within the previous 30 days patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated previous enrollment in this study

1. anticipated transfer to another hospital (which is not a study site) within 72 hours 2. allergy or contraindications to tnk 3. contraindications to systemic anticoagulation 4. active bleeding 5. known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. 6. major gi or gu bleed within the past 3 weeks 7. history of hemorrhagic stroke 8. history of acute ischemic stroke in the last 90 days 9. high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). 10. pe associated with syncope and any degree of head trauma 11. pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. 12. administration of thrombolytic agent within the previous 7 days 13. pulmonary thrombectomy within the previous 30 days 14. uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization 15. severe ards (p/f ratio < 100) 16. platelet count lower than 80,000/mm3 17. known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 18. arterial puncture at a non-compressible site within the past 5 days 19. prior brain surgery 20. severe trauma in the prior 2 weeks 21. major surgery in the prior 2 weeks 22. brain malignancy / metastases, brain tumor in past 5 years 23. brain avm or ruptured aneurysm at any time 24. acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization 25. cardiac tamponade 26. lumbar puncture with in past 7 days 27. known abdominal or thoracic aneurysm 28. acute or chronic renal failure requiring dialysis 29. chronic liver failure (acutely elevated liver function tests not an exclusion criterion) 30. bacterial endocarditis at time of study entry 31. seizure during pre-hospital course or during hospitalization for covid-19 32. currently on ecmo 33. pregnancy, lactation or parturition within the previous 30 days 34. patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. 35. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated 36. previous enrollment in this study

1. anticipated transfer to another hospital (which is not a study site) within 72 hours 2. allergy or contraindications to tnk 3. contraindications to systemic anticoagulation 4. active bleeding 5. known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate. 6. major gi or gu bleed within the past 3 weeks 7. history of hemorrhagic stroke 8. history of acute ischemic stroke in the last 90 days 9. high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). 10. pe associated with syncope and any degree of head trauma 11. pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. 12. administration of thrombolytic agent within the previous 7 days 13. pulmonary thrombectomy within the previous 30 days 14. uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization 15. severe ards (p/f ratio < 100) 16. platelet count lower than 80,000/mm3 17. known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 18. arterial puncture at a non-compressible site within the past 5 days 19. prior brain surgery 20. severe trauma in the prior 2 weeks 21. major surgery in the prior 2 weeks 22. brain malignancy / metastases, brain tumor in past 5 years 23. brain avm or ruptured aneurysm at any time 24. acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization 25. cardiac tamponade 26. lumbar puncture with in past 7 days 27. known abdominal or thoracic aneurysm 28. acute or chronic renal failure requiring dialysis 29. chronic liver failure (acutely elevated liver function tests not an exclusion criterion) 30. bacterial endocarditis at time of study entry 31. seizure during pre-hospital course or during hospitalization for covid-19 32. currently on ecmo 33. pregnancy, lactation or parturition within the previous 30 days 34. patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. 35. any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated 36. previous enrollment in this study

- age ≥ 75 years - anticipated transfer to another hospital which is not a study site within 72 hours - allergy or contraindications to tnk - contraindications to systemic anticoagulation - active bleeding - known significant bleeding risk (recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion) - while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate - high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). - pe associated with syncope and any degree of head trauma - pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. - administration of thrombolytic agent within the previous 7 days - pulmonary thrombectomy within the previous 30 days - uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization - previous enrollment in this study - pregnancy, lactation or parturition within the previous 30 days - platelet count lower than 80,000/mm3 - prior brain surgery - severe trauma in the prior 2 weeks - major surgery in the prior 2 weeks - brain malignancy / metastases, brain tumor in past 5 years - brain avm or ruptured aneurysm at any time - any intracranial pathology that the investigator / consultants feel would place the patient at increased risk if the investigational therapy were initiated (non-contrast head ct must be performed to exclude acute intracranial pathology [e.g. stroke] if patient is intubated and neurologic exam cannot be performed satisfactorily) - acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization - acute or chronic renal failure requiring dialysis - chronic liver failure (acutely elevated liver function tests not an exclusion criterion) - cardiac tamponade - bacterial endocarditis at time of study entry - seizure during pre-hospital course or during hospitalization for covid-19 - currently on ecmo - patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. - severe ards (p/f ratio < 100) - major gi or gu bleed within the past 3 weeks - arterial puncture at a non-compressible site within the past 5 days - lumbar puncture with in past 7 days - known abdominal or thoracic aneurysm - known hypersensitivity or allergy to any ingredients of tenecteplase - history of acute ischemic stroke in the last 90 days - history of hemorrhagic stroke - pregnant - known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 - any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated

- age ≥ 75 years - anticipated transfer to another hospital which is not a study site within 72 hours - allergy or contraindications to tnk - contraindications to systemic anticoagulation - active bleeding - known significant bleeding risk (recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion) - while there is no specific hemoglobin cut-off value for enrollment, investigators will gauge the severity / stability of the hgb and exclude patients deemed inappropriate - high-risk (massive) acute pe (pe associated with hypotension (systolic bp < 90 mmhg for > 15 min). - pe associated with syncope and any degree of head trauma - pe meeting criteria for intermediate-risk pe and thus for enrollment, but with clinical evidence of deterioration such that the investigator deems the patient not appropriate for enrollment. - administration of thrombolytic agent within the previous 7 days - pulmonary thrombectomy within the previous 30 days - uncontrolled hypertension defined as systolic blood pressure >180 mm hg and/or diastolic blood pressure >110 mm hg at randomization - previous enrollment in this study - pregnancy, lactation or parturition within the previous 30 days - platelet count lower than 80,000/mm3 - prior brain surgery - severe trauma in the prior 2 weeks - major surgery in the prior 2 weeks - brain malignancy / metastases, brain tumor in past 5 years - brain avm or ruptured aneurysm at any time - any intracranial pathology that the investigator / consultants feel would place the patient at increased risk if the investigational therapy were initiated (non-contrast head ct must be performed to exclude acute intracranial pathology [e.g. stroke] if patient is intubated and neurologic exam cannot be performed satisfactorily) - acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization - acute or chronic renal failure requiring dialysis - chronic liver failure (acutely elevated liver function tests not an exclusion criterion) - cardiac tamponade - bacterial endocarditis at time of study entry - seizure during pre-hospital course or during hospitalization for covid-19 - currently on ecmo - patients, in whom, in the opinion of the investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit. - severe ards (p/f ratio < 100) - major gi or gu bleed within the past 3 weeks - arterial puncture at a non-compressible site within the past 5 days - lumbar puncture with in past 7 days - known abdominal or thoracic aneurysm - known hypersensitivity or allergy to any ingredients of tenecteplase - history of acute ischemic stroke in the last 90 days - history of hemorrhagic stroke - pregnant - known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr >1.7 - any other condition that the investigator felt would place the patient at increased risk if the investigational therapy were initiated