COVID-19Phase 2NCT04505592
Tenecteplase in Patients With COVID-19
A Phase 2 study testing Tenecteplase in people with COVID-19 and Respiratory Failure, run by Hooman Poor at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID-19, Respiratory Failure, ARDS
- What is being tested?
- Tenecteplase
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2020to 10 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 27Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure 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.
Read the 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
- Being tested
- Tenecteplase, Placebo
- Keywords
- COVID-19, ARDS, thrombolysis, tenecteplase
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenecteplaseDrug
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.
PlaceboDrug
Patients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Tenecteplase |
| Placebo | Placebo comparator | Placebo control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 Days
Number of Participants With Occurrences of Bleeding
Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding
Measured: 28 days
Secondary outcomes (11)
Number of Participants With In-hospital Deaths at 14 Days
Number of patients who expired in the hospital within the first 14 days of their participation in the study
Measured: 14 days
Number of Participants With Death at 28 Days
Number of participants who expired by 28 days/end of study
Measured: 28 days
Number of Ventilator-free Days
Number of ventilator-free days in 28 days period
Measured: 28 days
Number of Respiratory Failure-free Days
Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.
Measured: 28 days
Number of Vasopressor-free Days
Number of vasopressor-free days over 28 days period
Measured: 28 days
Number of Vasopressor Doses at 24 Hours
Measured: 24 hours and 72 hours
P/F Ratio
The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).
Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving.
Normal P/F Ratio is ≥ 400.
300 to 200 is considered mild ARDS
200 to 100 is considered moderate ARDS
Anything below 100 is considered severe ARDS.
Measured: 24 hours and 72 hours
Number of ICU-free Days
Number of days the patient spent outside the ICU
Measured: 28 days
Hospital Length of Stay
Length of time the patient spent in the hospital, including ICU
Measured: up to 29 days
Number of Participants With New-onset Renal Failure
Number of patients who experienced renal failure during the course of the study
Measured: 28 days
Number of Participants With Need for Renal Replacement Therapy
Number of patients who underwent renal replacement treatment for their renal failure
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start25 Sep 2020
- Primary completion10 Mar 2022
- Study completion10 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hooman Poor
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, Hooman Poor, Icahn School of Medicine at Mount Sinai
- Investigators
- Hooman Poor, MD, Principal investigator, Icahn School of Medicine at Mount SinaiJ Mocco, MD, Study director, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04505592
- Sponsor's protocol ID
- GCO 20-1764
- Status last verified
- Apr 2023
- First submitted
- 6 Aug 2020
- Last updated
- 6 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure in Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04505592
- Acronym / sponsor ID
- GCO 20-1764
- Conditions
- COVID-19, Respiratory Failure, ARDS
- Keywords
- COVID-19, ARDS, thrombolysis, tenecteplase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Hooman PoorUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- 10 Mar 2022 (actual)
- Study completion
- 10 Mar 2022 (actual)
- First posted
- 10 Aug 2020 (actual)
- Results
- Posted 6 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Tenecteplase | Experimental | Drug: TenecteplaseFirst 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 | Placebo comparator | Drug: PlaceboPlacebo control |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (27 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TenecteplaseFirst 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. | Drug | Tenecteplase |
| PlaceboPatients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal. | Drug | Placebo |
Primary outcome
Number of Participants Free of Respiratory Failure
Time frame: 28 Days
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
Number of Participants With Occurrences of Bleeding
Time frame: 28 days
Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding
11 secondary outcomes
Number of Participants With In-hospital Deaths at 14 Days
Time frame: 14 days
Number of Participants With Death at 28 Days
Time frame: 28 days
Number of Ventilator-free Days
Time frame: 28 days
Number of Respiratory Failure-free Days
Time frame: 28 days
Number of Vasopressor-free Days
Time frame: 28 days
Number of Vasopressor Doses at 24 Hours
Time frame: 24 hours and 72 hours
P/F Ratio
Time frame: 24 hours and 72 hours
Number of ICU-free Days
Time frame: 28 days
Hospital Length of Stay
Time frame: up to 29 days
Number of Participants With New-onset Renal Failure
Time frame: 28 days
Number of Participants With Need for Renal Replacement Therapy
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hooman Poor, MD principal investigator
Icahn School of Medicine at Mount Sinai
J Mocco, MD study director
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tenecteplase in people with COVID-19 and Respiratory Failure, run by Hooman Poor at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Free of Respiratory Failure (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2023.