Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism
NCT ID: NCT04558125
Last Updated: 2021-10-26
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
TERMINATED
Clinical Phase
PHASE4
Total Enrollment
2 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-09-08
Study Completion Date
2021-08-08
Brief Summary
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* 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
* 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
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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.
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
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Pulmonary Embolism
COVID
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Study Groups
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Low-dose TNKase and Standard of Care Anticoagulation
1. TNKase (0.25 mg/kg) bolus Other names: Tenecteplase, TNK
2. Standard of care anticoagulation (heparin or enoxaparin)
Group Type
EXPERIMENTAL
TNKase
Intervention Type
DRUG
Tenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
Enoxaparin
Intervention Type
DRUG
All participants must also receive standard of care anticoagulation therapy.
Placebo and and Standard of Care Anticoagulation
1. Placebo bolus (intravenous syringe identical to that of TNK )
2. Standard of care anticoagulation (heparin or enoxaparin)
Group Type
ACTIVE_COMPARATOR
Placebo
Intervention Type
DRUG
Placebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
Enoxaparin
Intervention Type
DRUG
All participants must also receive standard of care anticoagulation therapy.
Interventions
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TNKase
Tenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
Intervention Type
DRUG
Placebo
Placebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
Intervention Type
DRUG
Enoxaparin
All participants must also receive standard of care anticoagulation therapy.
Intervention Type
DRUG
Other Intervention Names
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Tenecteplase
TNK
Low molecular weight heparin
Lovenox
Enoxaparin sodium
Heparin
Heparin sodium
Eligibility Criteria
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Inclusion Criteria
1. Male or non-pregnant female adult ≥18 years of age, but \< 75 years of age at time of enrollment.
2. 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.
3. 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.
4. Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
5. 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.
2. 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.
3. 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.
4. Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
5. 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.
Exclusion Criteria
1. Anticipated transfer to another hospital (which is not a study site) within 72 hours
2. Allergy or contraindications to TNK
3. Contraindications to systemic anticoagulation
4. Active bleeding
5. 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.
6. Major GI or GU bleed within the past 3 weeks
7. History of hemorrhagic stroke
8. History of acute ischemic stroke in the last 90 days
9. High-risk (massive) acute PE (PE associated with hypotension (systolic BP \< 90 mmHg for \> 15 min).
10. PE associated with syncope and any degree of head trauma
11. 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.
12. Administration of thrombolytic agent within the previous 7 days
13. Pulmonary thrombectomy within the previous 30 days
14. Uncontrolled hypertension defined as systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>110 mm Hg at randomization
15. Severe ARDS (P/F ratio \< 100)
16. Platelet count lower than 80,000/mm3
17. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \>1.7
18. Arterial puncture at a non-compressible site within the past 5 days
19. Prior brain surgery
20. Severe trauma in the prior 2 weeks
21. Major surgery in the prior 2 weeks
22. Brain malignancy / metastases, brain tumor in past 5 years
23. Brain AVM or ruptured aneurysm at any time
24. Acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization
25. Cardiac tamponade
26. Lumbar puncture with in past 7 days
27. Known abdominal or thoracic aneurysm
28. Acute or chronic renal failure requiring dialysis
29. Chronic liver failure (acutely elevated liver function tests not an exclusion criterion)
30. Bacterial endocarditis at time of study entry
31. Seizure during pre-hospital course or during hospitalization for COVID-19
32. Currently on ECMO
33. Pregnancy, lactation or parturition within the previous 30 days
34. Patients, in whom, in the opinion of the Investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit.
35. Any other condition that the Investigator felt would place the patient at increased risk if the investigational therapy were initiated
36. Previous enrollment in this study
2. Allergy or contraindications to TNK
3. Contraindications to systemic anticoagulation
4. Active bleeding
5. 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.
6. Major GI or GU bleed within the past 3 weeks
7. History of hemorrhagic stroke
8. History of acute ischemic stroke in the last 90 days
9. High-risk (massive) acute PE (PE associated with hypotension (systolic BP \< 90 mmHg for \> 15 min).
10. PE associated with syncope and any degree of head trauma
11. 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.
12. Administration of thrombolytic agent within the previous 7 days
13. Pulmonary thrombectomy within the previous 30 days
14. Uncontrolled hypertension defined as systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>110 mm Hg at randomization
15. Severe ARDS (P/F ratio \< 100)
16. Platelet count lower than 80,000/mm3
17. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \>1.7
18. Arterial puncture at a non-compressible site within the past 5 days
19. Prior brain surgery
20. Severe trauma in the prior 2 weeks
21. Major surgery in the prior 2 weeks
22. Brain malignancy / metastases, brain tumor in past 5 years
23. Brain AVM or ruptured aneurysm at any time
24. Acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization
25. Cardiac tamponade
26. Lumbar puncture with in past 7 days
27. Known abdominal or thoracic aneurysm
28. Acute or chronic renal failure requiring dialysis
29. Chronic liver failure (acutely elevated liver function tests not an exclusion criterion)
30. Bacterial endocarditis at time of study entry
31. Seizure during pre-hospital course or during hospitalization for COVID-19
32. Currently on ECMO
33. Pregnancy, lactation or parturition within the previous 30 days
34. Patients, in whom, in the opinion of the Investigator, are critically ill from concomitant comorbid cardiopulmonary disease, and unlikely to benefit.
35. Any other condition that the Investigator felt would place the patient at increased risk if the investigational therapy were initiated
36. Previous enrollment in this study
Minimum Eligible Age
18 Years
Maximum Eligible Age
75 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Genentech, Inc.
INDUSTRY
Sponsor Role
collaborator
Cedars-Sinai Medical Center
OTHER
Sponsor Role
lead
Responsible Party
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Victor Tapson, MD
Professor of Medicine
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Victor E Tapson, MD
Role: PRINCIPAL_INVESTIGATOR
Cedars-Sinai Medical Center
Locations
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Cedars-Sinai Medical Center
Los Angeles, California, United States
Site Status
Countries
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United States
References
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BACKGROUND
Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e67-e492. doi: 10.1161/CIR.0000000000000558. Epub 2018 Jan 31. No abstract available.
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BACKGROUND
Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.
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BACKGROUND
Bivard A, Huang X, McElduff P, Levi CR, Campbell BC, Cheripelli BK, Kalladka D, Moreton FC, Ford I, Bladin CF, Davis SM, Donnan GA, Muir KW, Parsons MW. Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials. Circulation. 2017 Jan 31;135(5):440-448. doi: 10.1161/CIRCULATIONAHA.116.022582. Epub 2016 Dec 13.
Reference Type
BACKGROUND
Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
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BACKGROUND
From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO); Sacks D, Baxter B, Campbell BCV, Carpenter JS, Cognard C, Dippel D, Eesa M, Fischer U, Hausegger K, Hirsch JA, Shazam Hussain M, Jansen O, Jayaraman MV, Khalessi AA, Kluck BW, Lavine S, Meyers PM, Ramee S, Rufenacht DA, Schirmer CM, Vorwerk D. Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. Int J Stroke. 2018 Aug;13(6):612-632. doi: 10.1177/1747493018778713. Epub 2018 May 22. No abstract available.
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BACKGROUND
Churilov L, Arnup S, Johns H, Leung T, Roberts S, Campbell BC, Davis SM, Donnan GA. An improved method for simple, assumption-free ordinal analysis of the modified Rankin Scale using generalized odds ratios. Int J Stroke. 2014 Dec;9(8):999-1005. doi: 10.1111/ijs.12364. Epub 2014 Sep 4.
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BACKGROUND
Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.
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BACKGROUND
DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med. 1994 Jul 15-30;13(13-14):1341-52; discussion 1353-6. doi: 10.1002/sim.4780131308.
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Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.
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BACKGROUND
Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
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BACKGROUND
Haley EC Jr, Lyden PD, Johnston KC, Hemmen TM; TNK in Stroke Investigators. A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke. 2005 Mar;36(3):607-12. doi: 10.1161/01.STR.0000154872.73240.e9. Epub 2005 Feb 3.
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BACKGROUND
Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, Fanale C, Libman R, Kwiatkowski TG, Llinas RH, Levine SR, Johnston KC, Buchsbaum R, Levy G, Levin B; Tenecteplase in Stroke Investigators. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010 Apr;41(4):707-11. doi: 10.1161/STROKEAHA.109.572040. Epub 2010 Feb 25.
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BACKGROUND
Howard G, Waller JL, Voeks JH, Howard VJ, Jauch EC, Lees KR, Nichols FT, Rahlfs VW, Hess DC. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke. 2012 Mar;43(3):664-9. doi: 10.1161/STROKEAHA.111.632935. Epub 2012 Feb 16.
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BACKGROUND
Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7. Epub 2015 Feb 26.
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BACKGROUND
Huang X, MacIsaac R, Thompson JL, Levin B, Buchsbaum R, Haley EC Jr, Levi C, Campbell B, Bladin C, Parsons M, Muir KW. Tenecteplase versus alteplase in stroke thrombolysis: An individual patient data meta-analysis of randomized controlled trials. Int J Stroke. 2016 Jul;11(5):534-43. doi: 10.1177/1747493016641112. Epub 2016 Apr 5.
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BACKGROUND
Jovin TG, Liebeskind DS, Gupta R, Rymer M, Rai A, Zaidat OO, Abou-Chebl A, Baxter B, Levy EI, Barreto A, Nogueira RG. Imaging-based endovascular therapy for acute ischemic stroke due to proximal intracranial anterior circulation occlusion treated beyond 8 hours from time last seen well: retrospective multicenter analysis of 237 consecutive patients. Stroke. 2011 Aug;42(8):2206-11. doi: 10.1161/STROKEAHA.110.604223. Epub 2011 Jul 21.
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BACKGROUND
Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
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BACKGROUND
Kate M, Wannamaker R, Kamble H, Riaz P, Gioia LC, Buck B, Jeerakathil T, Smyth P, Shuaib A, Emery D, Butcher K. Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset. J Stroke. 2018 Jan;20(1):122-130. doi: 10.5853/jos.2017.00178. Epub 2018 Jan 31.
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BACKGROUND
Lansberg MG, Cereda CW, Mlynash M, Mishra NK, Inoue M, Kemp S, Christensen S, Straka M, Zaharchuk G, Marks MP, Bammer R, Albers GW; Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) Study Investigators. Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology. 2015 Aug 25;85(8):708-14. doi: 10.1212/WNL.0000000000001853. Epub 2015 Jul 29.
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BACKGROUND
Logallo N, Kvistad CE, Thomassen L. Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke. CNS Drugs. 2015;29(10):811-8. doi: 10.1007/s40263-015-0280-9.
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BACKGROUND
Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Ronning OM, Thommessen B, Amthor KF, Ihle-Hansen H, Kurz M, Tobro H, Kaur K, Stankiewicz M, Carlsson M, Morsund A, Idicula T, Aamodt AH, Lund C, Naess H, Waje-Andreassen U, Thomassen L. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3. Epub 2017 Aug 2.
Reference Type
BACKGROUND
Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.
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BACKGROUND
Parsons MW, Levi CR. Reperfusion trials for acute ischaemic stroke. Lancet. 2012 Aug 25;380(9843):706-8. doi: 10.1016/S0140-6736(12)61043-5. Epub 2012 Jun 28. No abstract available.
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BACKGROUND
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.
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BACKGROUND
Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Devlin TG, Lopes DK, Reddy V, du Mesnil de Rochemont R, Jahan R; SWIFT PRIME Investigators. Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke. Int J Stroke. 2015 Apr;10(3):439-48. doi: 10.1111/ijs.12459.
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BACKGROUND
Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC, Khavjou OA, Lackland DT, Lichtman JH, Mohl S, Sacco RL, Saver JL, Trogdon JG; American Heart Association Advocacy Coordinating Committee and Stroke Council. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013 Aug;44(8):2361-75. doi: 10.1161/STR.0b013e31829734f2. Epub 2013 May 22.
Reference Type
BACKGROUND
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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http://www.acc.org/latest-in-cardiology/ten-points-to-remember/2018/01/29/12/45/2018-guidelines-for-the-early-management-of-stroke
Stroke Early Management Guidelines
https://doi.org/10.1101/2020.04.30.20076703
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https://www.semanticscholar.org/paper/Generalized-Odds-Ratios-for-Ordinal-Data-Agresti/f7ac23e686de751706146f8dd926d1f03d1b0255
Generalized odds ratios for ordinal data
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
ML42522
Identifier Type: -
Identifier Source: org_study_id