Tenecteplase in Patients With COVID-19

NCT04505592 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 20-1764
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19; Respiratory Failure; ARDS

Keywords

COVID-19; ARDS; thrombolysis; tenecteplase

Outcome Measures

Primary Outcomes (2)

• Number of Participants Free of Respiratory Failure

  The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days

  28 Days

• Number of Participants With Occurrences of Bleeding

  Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding

  28 days

Secondary Outcomes (11)

• Number of Participants With In-hospital Deaths at 14 Days

  14 days

• Number of Participants With Death at 28 Days

  28 days

• Number of Ventilator-free Days

  28 days

• Number of Respiratory Failure-free Days

  28 days

• Number of Vasopressor-free Days

  28 days

Study Arms (2)

Tenecteplase

EXPERIMENTAL

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).

Drug: Tenecteplase

Placebo

PLACEBO COMPARATOR

Placebo control

Drug: Placebo

Interventions

Tenecteplase 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.

Tenecteplase

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hooman Poor: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Hooman Poor
• Organization: Icahn School of Medicine at Mount Sinai

hooman.poor@mountsinai.org

(212) 241-5656

Study Officials

• Hooman Poor, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• J Mocco, MD

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients and study investigators will be blinded to subject treatment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 10, 2020
• Study Start: September 25, 2020
• Primary Completion: March 10, 2022
• Study Completion: March 10, 2022
• Last Updated: April 6, 2023
• Results First Posted: April 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)