Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism

This is an interventional treatment trial for Pulmonary Embolism Read More

Inclusion Criteria:

1. Male or non-pregnant female adult ≥18 years of age, but < 75 years of age at time of enrollment.
2. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 28 days prior to randomization, OR person under investigation (PUI) of COVID-19 with pulmonary infiltrates and elevated ferritin and CRP level.

3. Acute intermediate-risk pulmonary embolism defined as:

   • Presence of acute pulmonary embolism confirmed by diagnostic imaging (computed tomographic angiography, ventilation-perfusion scan, or invasive pulmonary angiography) AND
   • Presence of clot burden with at least one lobar artery involved OR bilateral with at least segmental branches OR unilateral clot in at least multiple segmental branches.
4. Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
5. In the Investigator's judgement, patient has the ability to comply with the study protocol, and understands and agrees to comply with planned TNK bolus versus placebo.

Exclusion Criteria:

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