Tenecteplase in Patients With COVID-19
Tenecteplase in Patients With COVID-19
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.
Patients with COVID-19 who suffer from acute hypoxemic respiratory failure have a poor
 prognosis. COVID-19 has been associated with a hyperinflammatory and hypercoagulable state,
 leading to a range of thromboembolic complications from pulmonary embolism to ischemic
 stroke. Furthermore, emerging data suggest that the associated acute respiratory failure is,
 at least in part, due to pulmonary vascular disease caused by micro- and/or macro-emboli,
 creating pulmonary vascular shunting and dead-space ventilation. In this placebo-controlled,
 double blind, randomized, Phase II dose escalation study, we plan to evaluate the clinical
 efficacy and safety of low-dose IV bolus tenecteplase together with anticoagulation compared
 with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed
 with COVID-19 respiratory failure with elevated D-dimer. We believe these patients can be
 successfully treated without significantly increasing the risk of major bleeding while
 improving recovery rates, shorten hospitalization time, and perhaps ultimately prove to
 improve survival.
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