Tenecteplase in Patients With COVID-19

• Status: Enrolling by invitation
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a placebo-controlled, double blind, randomized, Phase II dose escalation study intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of COVID-19 associated respiratory failure. The hypothesis is that administration of the drug, in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hooman Poor
• Collaborator: Genentech, Inc.
• Treatments: Tenecteplase

Criteria

Inclusion Criteria

• Patient/legally authorized representative has completed the Informed Consent Form

• Age ≥18 years

• Ability to comply with the study protocol, in the investigator's judgment

• Respiratory failure secondary to COVID-19 requiring mechanical ventilation for no greater than 24 hours, or high-flow nasal cannula (HFNC),non-rebreather (NRB) mask or non-invasive positive pressure ventilation (NIPPV) for no greater than 48 hours

• Confirmed infection with SARS-CoV-2 virus (PCR positive within 14 days)

• Elevated D-dimer (>6 times upper limit of normal within past 72 hours)

• For patient who are intubated >12 hours prior to randomization or with any evidence of neurologic deficit a head CT within 12 hours demonstrating no evidence of acute or subacute infarct or hemorrhage

Exclusion Criteria

• Current participation in another investigational drug study within the prior 7 days

• Known hypersensitivity or allergy to any ingredients of tenecteplase

• Active internal bleeding

• Known bleeding diathesis

• Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)

• Treatment with a thrombolytic within the last 3 months prior to randomization (exception for the use of Cathflo alteplase for occlusions of central venous catheters)

• Baseline platelet count <80,000/L (results must be available prior to treatment)

• Baseline blood glucose >400 mg/dL (22.20 mmol/L)

• Baseline blood glucose <50 mg/dL needs to be normalized prior to randomization

• Intracranial or intraspinal surgery or trauma within 2 months

• Other, non-COVID-19 related, serious, advanced, or terminal illness (investigator judgment) or life expectancy is less than 6 months

• History of acute ischemic stroke in the last 90 days

• History of intracranial bleeding, including hemorrhagic stroke

• Presumed septic embolus; suspicion of bacterial endocarditis

• Mechanical ventilation > 24 hours, HFNC, NRB, NIPPV, or any combination, for greater than 48 hours

• Mechanical ventilation, HFNC, NRB, or NIPVV (for reasons other than obstructive sleep apnea) within the prior 30 days (excluding 48 hours prior to randomization)

• Moribund status suggesting imminent vascular collapse and inability to survive > 72 hours (investigator determination)

• Uncontrolled hypertension defined as systolic BP > 180 mm Hg and/or diastolic BP > 110 mm Hgb

• Age > 75 years

• History of traumatic brain injury within 2 months

• Recent head trauma with fracture or brain injury

• History of Heparin Induced Thrombocytopenia (HIT) and/or other hereditary or acquired hemorrhagic diathesis or coagulation factor deficiency

• INR > 2 or recent oral anticoagulant therapy with INR >1.7

• Pregnancy or lactation within the prior 30 days; women of childbearing age (<55 years old) should have documentation of a negative pregnancy test

• Chronic liver disease defined as > Childs-Pugh Class B

• Atrial fibrillation, mitral stenosis, or known left heart thrombosis

• Any other condition that, in the opinion of the investigator, precludes administration of tenecteplase or poses a significant hazard to the patient receives tenecteplase