Tenecteplase in Patients With COVID-19

NCT ID: NCT04505592

Last Updated: 2023-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-25
• Study Completion Date: 2022-03-10

Brief 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.

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.

Conditions

COVID-19; Respiratory Failure; ARDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Tenecteplase

Intervention Type: DRUG

First 20 patients randomized to treatment arm will receive 0.25 mg/kg of tenecteplase. Next 20 patients randomized to treatment arm will receive 0.50 mg/kg of tenecteplase. Both will receive concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.

Placebo

Placebo control

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.

Interventions

Tenecteplase

First 20 patients randomized to treatment arm will receive 0.25 mg/kg of tenecteplase. Next 20 patients randomized to treatment arm will receive 0.50 mg/kg of tenecteplase. Both will receive concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.

Intervention Type: DRUG

Placebo

Patients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Hooman Poor

OTHER

Sponsor Role: lead

Responsible Party

Hooman Poor

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hooman Poor, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

J Mocco, MD

Role: STUDY_DIRECTOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Hospital

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GCO 20-1764

Identifier Type: -

Identifier Source: org_study_id