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

• Status: Terminated
• Trial end date: 2021-08-08
• Target enrollment: 0
• Participant gender: All

Summary

• There is a knowledge gap associated with the management of patients with COVID-19 lung injury and a laboratory picture compatible with disseminated intravascular coagulation (DIC). Clinical data to date support that COVID-19 is associated with a prothrombotic state that is not simply explained by an influx of more critically ill individuals.

• These patients suffer from severe respiratory failure; hypoxemia and ventilator dependence are the primary concerns; ARDS with respiratory failure is frequently the cause of death. Macroscopic and probable microvascular thromboembolic events are a major concern in this population.

• When DIC is associated with COVID-19, it predicts a very poor prognosis.

• This study will evaluate the clinical efficacy and safety of low-dose IV bolus tenecteplase (TNK) together with anticoagulation compared with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed with COVID-19 and acute intermediate-risk PE.

• Prospective, multicenter, randomized two-arm trial enrolling consecutive patients who meet enrollment criteria.

• The study will generate evidence that low-dose TNK together with anticoagulation is beneficial in these patients

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cedars-Sinai Medical Center
• Collaborator: Genentech, Inc.
• Treatments: Calcium heparin; Dalteparin; Enoxaparin; Enoxaparin sodium; Heparin; Heparin, Low-Molecular-Weight; Tenecteplase; Tinzaparin

Criteria

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