Tenecteplase in Patients With COVID-19
Purpose
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.
Conditions
- COVID-19
- Respiratory Failure
- ARDS
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Subjects will be randomized in a 2:1 ratio to treatment or control in blocks of 15, performed twice per dose (low and high) with randomization stratified by site.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Patients and study investigators will be blinded to subject treatment.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Tenecteplase |
First 20 patients randomized to treatment will receive tenecteplase 0.25 mg/kg (maximum 25 mg). Last 20 patients randomized to treatment will receive tenecteplase 0.50 mg/kg (maximum 40 mg). |
|
|
Placebo Comparator Placebo |
Placebo control |
|
Recruiting Locations
More Details
- NCT ID
- NCT04505592
- Status
- Completed
- Sponsor
- Hooman Poor
Detailed Description
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.