Pulmonary EmbolismPhase 4NCT04558125
Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism
A Phase 4 study testing TNKase and Enoxaparin in people with Pulmonary Embolism and COVID, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
There is a knowledge gap associated with the management of patients with COVID-19 lung injury and a laboratory picture compatible with disseminated intravascular coagulation (DIC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Embolism, COVID
- What is being tested?
- TNKase and Enoxaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2020to 8 Aug 2021
- Phase
- Phase 4
- 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
- Male or non-pregnant female adult ≥18 years of age, but < 75 years of age at time of enrollment.
- Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 28 days prior to randomization, OR person under investigation (PUI) of COVID-19 with pulmonary infiltrates and elevated ferritin and CRP level.
- Acute intermediate-risk pulmonary embolism defined as:
- Presence of acute pulmonary embolism confirmed by diagnostic imaging (computed tomographic angiography, ventilation-perfusion scan, or invasive pulmonary angiography) AND
- Presence of clot burden with at least one lobar artery involved OR bilateral with at least segmental branches OR unilateral clot in at least multiple segmental branches.
- Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
- In the Investigator's judgement, patient has the ability to comply with the study protocol, and understands and agrees to comply with planned TNK bolus versus placebo.
Who cannot join
- Anticipated transfer to another hospital (which is not a study site) within 72 hours
- Allergy or contraindications to TNK
- Contraindications to systemic anticoagulation
- Active bleeding
- Known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). While there is no specific hemoglobin cut-off value for enrollment, Investigators will gauge the severity / stability of the Hgb and exclude patients deemed inappropriate.
- Major GI or GU bleed within the past 3 weeks
Show all 36Show fewer
- History of hemorrhagic stroke
- History of acute ischemic stroke in the last 90 days
- High-risk (massive) acute PE (PE associated with hypotension (systolic BP < 90 mmHg for > 15 min).
- PE associated with syncope and any degree of head trauma
- PE meeting criteria for intermediate-risk PE and thus for enrollment, but with clinical evidence of deterioration such that the Investigator deems the patient not appropriate for enrollment.
- Administration of thrombolytic agent within the previous 7 days
- Pulmonary thrombectomy within the previous 30 days
- Uncontrolled hypertension defined as systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg at randomization
- Severe ARDS (P/F ratio < 100)
- Platelet count lower than 80,000/mm3
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR >1.7
- Arterial puncture at a non-compressible site within the past 5 days
- Prior brain surgery
- Severe trauma in the prior 2 weeks
- Major surgery in the prior 2 weeks
- Brain malignancy / metastases, brain tumor in past 5 years
- Brain AVM or ruptured aneurysm at any time
- Acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization
- Cardiac tamponade
- Lumbar puncture with in past 7 days
- Known abdominal or thoracic aneurysm
- Acute or chronic renal failure requiring dialysis
- Chronic liver failure (acutely elevated liver function tests not an exclusion criterion)
- Bacterial endocarditis at time of study entry
- Seizure during pre-hospital course or during hospitalization for COVID-19
- Currently on ECMO
- Pregnancy, lactation or parturition within the previous 30 days
- Patients, in whom, in the opinion of the Investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit.
- Any other condition that the Investigator felt would place the patient at increased risk if the investigational therapy were initiated
- Previous enrollment in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Low-Dose Tenecteplase in Covid-19 Patients With Acute Pulmonary Embolism: A Randomized, Double-Blind, Placebo-Controlled Trial
- There is a knowledge gap associated with the management of patients with COVID-19 lung injury and a laboratory picture compatible with disseminated intravascular coagulation (DIC). Clinical data to date support that COVID-19 is associated with a prothrombotic state that is not simply explained by an influx of more critically ill individuals.
- These patients suffer from severe respiratory failure; hypoxemia and ventilator dependence are the primary concerns; ARDS with respiratory failure is frequently the cause of death. Macroscopic and probable microvascular thromboembolic events are a major concern in this population.
- When DIC is associated with COVID-19, it predicts a very poor prognosis.
- This study will evaluate the clinical efficacy and safety of low-dose IV bolus tenecteplase (TNK) together with anticoagulation compared with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed with COVID-19 and acute intermediate-risk PE.
- Prospective, multicenter, randomized two-arm trial enrolling consecutive patients who meet enrollment criteria.
- The study will generate evidence that low-dose TNK together with anticoagulation is beneficial in these patients
Read the detailed description
This is a prospective, double-blind, placebo-controlled study randomizing patients with acute intermediate-risk PE who meet enrollment criteria in a 2:1 manner into intervention (TNK) versus placebo arms, respectively. There will be up to 6 sites. After 18 patients are enrolled, a safety assessment will be performed by an independent Data and Safety Monitoring Board, and if a safety issue arises, it will be considered and discussed among the investigators. The planned sample size is 45 patients (30 treatment and 15 control). Subjects will be assessed daily while hospitalized. Subjects discharged from the hospital will be asked to attend study visits at Days 14 and 30 (telephone / telemedicine, clinic or inpatient ward).
The overall objective of the study is to evaluate the clinical efficacy and safety of IV bolus tenecteplase (TNK) and therapeutic anticoagulation compared with placebo and therapeutic anticoagulation in hospitalized adults diagnosed with COVID-19 infection and acute intermediate-risk PE.
Written informed consent for participation in the study must be obtained before performing any study-related procedures (including screening evaluations). Informed Consent Forms for enrolled patients and for patients who are not subsequently enrolled will be maintained at the study site.
After informed consent is obtained, screening assessment will be completed to confirm a patient's eligibility for participation in the study. The screening visit will include medical history, physical exam and vital signs. Standard of care (SOC). labs will be reviewed. These may include INR, aPTT, PT (if patient is currently taking an anticoagulant), CBC with diff, comprehensive chemistry panel, D-dimer and Ferritin. The results of the SARS-CoV-2 will be documented. If subject is in child-bearing age and a pregnancy test was not done for SOC, a urine pregnancy test will be performed. Electrocadiogram and CTA will be reviewed.
If the patient is determined to be eligible, the study site will obtain the patient's medical record number/unique patient identification number, and treatment assignment to either interventional (TNK) or placebo will be randomly determined. Patients will be allocated to the interventional versus placebo arms in a 2:1 manner as per a computer-generated randomization schedule using permuted blocks of random sizes. The block sizes will not be disclosed to ensure concealment. A total of 30 TNK subjects versus 15 placebo controls will be enrolled.
Before the study drug/placebo is administered, the following labs will be drawn CBC with diff, comprehensive metabolic panel, CRP, Ferritin, IL-6, Fibrinogen, D-dimer, PT/PTT, LDH, lactate, troponin, creatinine kinase, and Thromboelastography (TEG). Vital signs and echocardiogram will be obtained. Shock Index will be calculated, then the infusion will begin.
Within 10 minutes (+ 5min) of infusion, a second TEG will be collected. At 6 hours after the infusion, a second Shock Index will be calculated. At 24+/- 6 hours after the bolus, a physical exam will be performed, vital signs will be collected, an echocardiogram will be performed and D-dimer, CRP, IL-6, and Ferritin will be done. TEG will be an optional addition to the 24-hour labs. Daily safety labs will include CBC and chemistry panel. SOC lab results will be collected from the chart.
Patients will have follow-up visits on Day 14 +/- 2 days and Day 30 +/- 4 days. These visits may take place via televisit or in person. Data will be collected on adverse events, vital signs and new concomitant medications. Safety labs will be obtained if visit occurs in person.
- Conditions
- Pulmonary Embolism, COVID
- Being tested
- TNKase, Placebo, Enoxaparin
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNKaseDrug
Also called Tenecteplase, TNK
Tenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
PlaceboDrug
Placebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
EnoxaparinDrug
Also called Low molecular weight heparin, Lovenox, Enoxaparin sodium, Heparin
All participants must also receive standard of care anticoagulation therapy.
| Study group | Role | What they receive |
|---|---|---|
| Low-dose TNKase and Standard of Care Anticoagulation | Experimental | 1. TNKase (0.25 mg/kg) bolus Other names: Tenecteplase, TNK
2. Standard of care anticoagulation (heparin or enoxaparin) Receives: Drug: TNKase; Drug: Enoxaparin |
| Placebo and and Standard of Care Anticoagulation | Active comparator | 1. Placebo bolus (intravenous syringe identical to that of TNK )
2. Standard of care anticoagulation (heparin or enoxaparin) Receives: Drug: Placebo; Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Improvement in Shock Index (Defined as Heart Rate Divided by Systolic Blood Pressure) 6 Hours After the TNK/Placebo Bolus.
For example, a patient may start with a heart rate of 100 beats/min and systolic blood pressure of 100 mm Hg (shock index = 1) and after therapy there may be an improvement where the heart rate is 90 beats/min, with systolic blood pressure of 110 mm Hg (shock index of 0.81), an improvement of 19%. A normal shock index is between 0.5 and 0.7 in healthy patients.
Measured: 6 hours post TNK/placebo infusion
Secondary outcomes (1)
1. Clinical Status at 24 Hours After Administration of TNK / Placebo Based Upon 7-point Scale.
Assessment of patient status using an ordinal scale will be recorded at baseline and once daily in the morning while hospitalized.
Level 1: Discharged (or "ready for discharge" on ambient air or < 2L suppl O2) Level 2: Non-ICU hospital ward (or "ready for hospital ward") not requiring suppl O2 Level 3: Non-ICU hospital ward (or "ready for hospital ward") requiring suppl O2 Level 4. ICU or non-ICU, requiring non-invasive ventilation or high-flow O2 Level 5. ICU, requiring intubation and mechanical ventilation Level 6: ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy) Level 7: Death
Measured: 24 +/- 6 hours post TNK/placebo infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2020
- Study start8 Sep 2020
- Primary completion10 Jul 2021
- Study completion8 Aug 2021
Why it stopped: Identification of eligible patients was slower than anticipated.
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.
- Publications (57)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Victor Tapson, MD, Cedars-Sinai Medical Center
- Investigators
- Victor E Tapson, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04558125
- Sponsor's protocol ID
- ML42522
- Status last verified
- Oct 2021
- First submitted
- 19 Sep 2020
- Last updated
- 26 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Morens DM, Daszak P, Taubenberger JK. Escaping Pandora's Box - Another Novel Coronavirus. N Engl J Med. 2020 Apr 2;382(14):1293-1295. doi: 10.1056/NEJMp2002106. Epub 2020 Feb 26. No abstract available.
PubMed 32101660Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
PubMed 32073213Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 Jun 25;58(7):1116-1120. doi: 10.1515/cclm-2020-0188.
PubMed 32172226Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
PubMed 32031570Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
PubMed 32105632Sebag SC, Bastarache JA, Ware LB. Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome. Curr Pharm Biotechnol. 2011 Sep;12(9):1481-96. doi: 10.2174/138920111798281171.
PubMed 21401517Ware LB, Bastarache JA, Wang L. Coagulation and fibrinolysis in human acute lung injury--new therapeutic targets? Keio J Med. 2005 Sep;54(3):142-9. doi: 10.2302/kjm.54.142.
PubMed 16237276Finigan JH. The coagulation system and pulmonary endothelial function in acute lung injury. Microvasc Res. 2009 Jan;77(1):35-8. doi: 10.1016/j.mvr.2008.09.002. Epub 2008 Sep 18.
PubMed 18938186Idell S, Koenig KB, Fair DS, Martin TR, McLarty J, Maunder RJ. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol. 1991 Oct;261(4 Pt 1):L240-8. doi: 10.1152/ajplung.1991.261.4.L240.
PubMed 1928357Prabhakaran P, Ware LB, White KE, Cross MT, Matthay MA, Olman MA. Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L20-8. doi: 10.1152/ajplung.00312.2002. Epub 2003 May 2.
PubMed 12730079Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med. 2007 Aug;35(8):1821-8. doi: 10.1097/01.CCM.0000221922.08878.49.
PubMed 17667242Moalli R, Doyle JM, Tahhan HR, Hasan FM, Braman SS, Saldeen T. Fibrinolysis in critically ill patients. Am Rev Respir Dis. 1989 Aug;140(2):287-93. doi: 10.1164/ajrccm/140.2.287.
PubMed 2504087Texereau J, Pene F, Chiche JD, Rousseau C, Mira JP. Importance of hemostatic gene polymorphisms for susceptibility to and outcome of severe sepsis. Crit Care Med. 2004 May;32(5 Suppl):S313-9. doi: 10.1097/01.ccm.0000126363.46191.dc.
PubMed 15118537Hardaway RM, Williams CH, Marvasti M, Farias M, Tseng A, Pinon I, Yanez D, Martinez M, Navar J. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med. 1990 Dec;18(12):1413-8. doi: 10.1097/00003246-199012000-00021.
PubMed 2123144Hart DA, Whidden P, Green F, Henkin J, Woods DE. Partial reversal of established bleomycin-induced pulmonary fibrosis by rh-urokinase in a rat model. Clin Invest Med. 1994 Apr;17(2):69-76.
PubMed 7516275
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Dose Tenecteplase in Covid-19 Patients With Acute Pulmonary Embolism: A Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT04558125
- Acronym / sponsor ID
- ML42522
- Conditions
- Pulmonary Embolism, COVID
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Identification of eligible patients was slower than anticipated.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 8 Sep 2020 (actual)
- Primary completion
- 10 Jul 2021 (actual)
- Study completion
- 8 Aug 2021 (actual)
- First posted
- 22 Sep 2020 (actual)
- Results
- Posted 26 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- There is a knowledge gap associated with the management of patients with COVID-19 lung injury and a laboratory picture compatible with disseminated intravascular coagulation (DIC). Clinical data to date support that COVID-19 is associated with a prothrombotic state that is not simply explained by an influx of more critically ill individuals.
- These patients suffer from severe respiratory failure; hypoxemia and ventilator dependence are the primary concerns; ARDS with respiratory failure is frequently the cause of death. Macroscopic and probable microvascular thromboembolic events are a major concern in this population.
- When DIC is associated with COVID-19, it predicts a very poor prognosis.
- This study will evaluate the clinical efficacy and safety of low-dose IV bolus tenecteplase (TNK) together with anticoagulation compared with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed with COVID-19 and acute intermediate-risk PE.
- Prospective, multicenter, randomized two-arm trial enrolling consecutive patients who meet enrollment criteria.
- The study will generate evidence that low-dose TNK together with anticoagulation is beneficial in these patients
Detailed description
This is a prospective, double-blind, placebo-controlled study randomizing patients with acute intermediate-risk PE who meet enrollment criteria in a 2:1 manner into intervention (TNK) versus placebo arms, respectively. There will be up to 6 sites. After 18 patients are enrolled, a safety assessment will be performed by an independent Data and Safety Monitoring Board, and if a safety issue arises, it will be considered and discussed among the investigators. The planned sample size is 45 patients (30 treatment and 15 control). Subjects will be assessed daily while hospitalized. Subjects discharged from the hospital will be asked to attend study visits at Days 14 and 30 (telephone / telemedicine, clinic or inpatient ward).
The overall objective of the study is to evaluate the clinical efficacy and safety of IV bolus tenecteplase (TNK) and therapeutic anticoagulation compared with placebo and therapeutic anticoagulation in hospitalized adults diagnosed with COVID-19 infection and acute intermediate-risk PE.
Written informed consent for participation in the study must be obtained before performing any study-related procedures (including screening evaluations). Informed Consent Forms for enrolled patients and for patients who are not subsequently enrolled will be maintained at the study site.
After informed consent is obtained, screening assessment will be completed to confirm a patient's eligibility for participation in the study. The screening visit will include medical history, physical exam and vital signs. Standard of care (SOC). labs will be reviewed. These may include INR, aPTT, PT (if patient is currently taking an anticoagulant), CBC with diff, comprehensive chemistry panel, D-dimer and Ferritin. The results of the SARS-CoV-2 will be documented. If subject is in child-bearing age and a pregnancy test was not done for SOC, a urine pregnancy test will be performed. Electrocadiogram and CTA will be reviewed.
If the patient is determined to be eligible, the study site will obtain the patient's medical record number/unique patient identification number, and treatment assignment to either interventional (TNK) or placebo will be randomly determined. Patients will be allocated to the interventional versus placebo arms in a 2:1 manner as per a computer-generated randomization schedule using permuted blocks of random sizes. The block sizes will not be disclosed to ensure concealment. A total of 30 TNK subjects versus 15 placebo controls will be enrolled.
Before the study drug/placebo is administered, the following labs will be drawn CBC with diff, comprehensive metabolic panel, CRP, Ferritin, IL-6, Fibrinogen, D-dimer, PT/PTT, LDH, lactate, troponin, creatinine kinase, and Thromboelastography (TEG). Vital signs and echocardiogram will be obtained. Shock Index will be calculated, then the infusion will begin.
Within 10 minutes (+ 5min) of infusion, a second TEG will be collected. At 6 hours after the infusion, a second Shock Index will be calculated. At 24+/- 6 hours after the bolus, a physical exam will be performed, vital signs will be collected, an echocardiogram will be performed and D-dimer, CRP, IL-6, and Ferritin will be done. TEG will be an optional addition to the 24-hour labs. Daily safety labs will include CBC and chemistry panel. SOC lab results will be collected from the chart.
Patients will have follow-up visits on Day 14 +/- 2 days and Day 30 +/- 4 days. These visits may take place via televisit or in person. Data will be collected on adverse events, vital signs and new concomitant medications. Safety labs will be obtained if visit occurs in person.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose TNKase and Standard of Care Anticoagulation | Experimental | Drug: TNKase, Drug: Enoxaparin1. TNKase (0.25 mg/kg) bolus Other names: Tenecteplase, TNK 2. Standard of care anticoagulation (heparin or enoxaparin) |
| Placebo and and Standard of Care Anticoagulation | Active comparator | Drug: Placebo, Drug: Enoxaparin1. Placebo bolus (intravenous syringe identical to that of TNK ) 2. Standard of care anticoagulation (heparin or enoxaparin) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or non-pregnant female adult ≥18 years of age, but < 75 years of age at time of enrollment.
- Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 28 days prior to randomization, OR person under investigation (PUI) of COVID-19 with pulmonary infiltrates and elevated ferritin and CRP level.
- Acute intermediate-risk pulmonary embolism defined as:
- Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
- In the Investigator's judgement, patient has the ability to comply with the study protocol, and understands and agrees to comply with planned TNK bolus versus placebo.
Key exclusion criteria (36 listed)
- Anticipated transfer to another hospital (which is not a study site) within 72 hours
- Allergy or contraindications to TNK
- Contraindications to systemic anticoagulation
- Active bleeding
- Known significant bleeding risk (although recent exposure to aspirin or any other antiplatelet therapy is not an exclusion criterion). While there is no specific hemoglobin cut-off value for enrollment, Investigators will gauge the severity / stability of the Hgb and exclude patients deemed inappropriate.
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 |
|---|---|---|
| TNKaseAlso: Tenecteplase, TNKTenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water. | Drug | Low-dose TNKase and Standard of Care Anticoagulation |
| PlaceboPlacebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water. | Drug | Placebo and and Standard of Care Anticoagulation |
| EnoxaparinAlso: Low molecular weight heparin, Lovenox, Enoxaparin sodium, HeparinAll participants must also receive standard of care anticoagulation therapy. | Drug | Low-dose TNKase and Standard of Care Anticoagulation, Placebo and and Standard of Care Anticoagulation |
Primary outcome
Percent Improvement in Shock Index (Defined as Heart Rate Divided by Systolic Blood Pressure) 6 Hours After the TNK/Placebo Bolus.
Time frame: 6 hours post TNK/placebo infusion
For example, a patient may start with a heart rate of 100 beats/min and systolic blood pressure of 100 mm Hg (shock index = 1) and after therapy there may be an improvement where the heart rate is 90 beats/min, with systolic blood pressure of 110 mm Hg (shock index of 0.81), an improvement of 19%. A normal shock index is between 0.5 and 0.7 in healthy patients.
1 secondary outcome
1. Clinical Status at 24 Hours After Administration of TNK / Placebo Based Upon 7-point Scale.
Time frame: 24 +/- 6 hours post TNK/placebo infusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32101660Morens DM, Daszak P, Taubenberger JK. Escaping Pandora's Box - Another Novel Coronavirus. N Engl J Med. 2020 Apr 2;382(14):1293-1295. doi: 10.1056/NEJMp2002106. Epub 2020 Feb 26. No abstract available.
- Background: PubMed 32073213Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
- Background: PubMed 32172226Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 Jun 25;58(7):1116-1120. doi: 10.1515/cclm-2020-0188.
- Background: PubMed 32031570Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
- Background: PubMed 32105632Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
- Background: PubMed 21401517Sebag SC, Bastarache JA, Ware LB. Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome. Curr Pharm Biotechnol. 2011 Sep;12(9):1481-96. doi: 10.2174/138920111798281171.
- Background: PubMed 16237276Ware LB, Bastarache JA, Wang L. Coagulation and fibrinolysis in human acute lung injury--new therapeutic targets? Keio J Med. 2005 Sep;54(3):142-9. doi: 10.2302/kjm.54.142.
- Background: PubMed 18938186Finigan JH. The coagulation system and pulmonary endothelial function in acute lung injury. Microvasc Res. 2009 Jan;77(1):35-8. doi: 10.1016/j.mvr.2008.09.002. Epub 2008 Sep 18.
- Background: PubMed 1928357Idell S, Koenig KB, Fair DS, Martin TR, McLarty J, Maunder RJ. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol. 1991 Oct;261(4 Pt 1):L240-8. doi: 10.1152/ajplung.1991.261.4.L240.
- Background: PubMed 12730079Prabhakaran P, Ware LB, White KE, Cross MT, Matthay MA, Olman MA. Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L20-8. doi: 10.1152/ajplung.00312.2002. Epub 2003 May 2.
- Background: PubMed 17667242Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med. 2007 Aug;35(8):1821-8. doi: 10.1097/01.CCM.0000221922.08878.49.
- Background: PubMed 2504087Moalli R, Doyle JM, Tahhan HR, Hasan FM, Braman SS, Saldeen T. Fibrinolysis in critically ill patients. Am Rev Respir Dis. 1989 Aug;140(2):287-93. doi: 10.1164/ajrccm/140.2.287.
- CDC Stroke FactsLink provided by the sponsor.
- Stroke Early Management GuidelinesLink provided by the sponsor.
- A randomized trial of anticoagulation strategies in COVID-19Link provided by the sponsor.
- Preventing COVID-19 complications with low- and high-dose anticoagulation (COVID-HEP)Link provided by the sponsor.
- Trial evaluating efficacy and safety of anticoagulation in patients with COVID-19 infection, nested in the Corimmuno-19 Cohort (CORIMMUNO-COAG)Link provided by the sponsor.
- Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19)Link provided by the sponsor.
- 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.
Victor E Tapson, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TNKase and Enoxaparin in people with Pulmonary Embolism and COVID, run by Cedars-Sinai Medical Center 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 36 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: stopped early, as of the sponsor's last update on 26 Oct 2021. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 26 Oct 2021). 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?
Percent Improvement in Shock Index (Defined as Heart Rate Divided by Systolic Blood Pressure) 6 Hours After the TNK/Placebo Bolus. (time frame: 6 hours post TNK/placebo infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04558125, which also lists 57 linked publications.
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 26 Oct 2021.