Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke
NCT ID: NCT03519737
Last Updated: 2018-11-30
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Clinical Phase
NA
Total Enrollment
596 participants
Study Classification
INTERVENTIONAL
Study Start Date
2018-08-17
Study Completion Date
2021-12-31
Brief Summary
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This is a randomized, placebo controlled, double-blind phase 3 clinical study to evaluate the efficacy and safety of transcranial ultrasound (TUS) using the Sonolysis Headframe as an adjunctive therapy to intravenous (IV) tissue plasminogen activator (tPA) therapy in subjects with acute ischemic stroke that initially present at non-endovascular (EVT) treating hospitals that have established transport services in place to transfer subjects to hospitals capable of performing EVT.
Detailed Description
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The primary objective of this study is to assess the safety and efficacy of TUS using the Sonolysis Headframe in combination with systemic tPA (Treatment group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke.
Number of Subjects Required:
Lead-in Phase: 40 subjects in the U.S.; Primary Phase: 556 total enrolled subjects (278 per arm)
Number of Study Centers:
Lead-in Phase: Up to 20 Institutions in U.S.; Primary Phase: Up to 70 Institutions worldwide
Number of Subjects Required:
Lead-in Phase: 40 subjects in the U.S.; Primary Phase: 556 total enrolled subjects (278 per arm)
Number of Study Centers:
Lead-in Phase: Up to 20 Institutions in U.S.; Primary Phase: Up to 70 Institutions worldwide
Conditions
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Acute Ischemic Stroke
Keywords
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Stroke
Acute Stroke
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Sham control and active insonation. During lead-in phase for the first 40 subjects, only active insonation will be programmed.
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Blinding is achieved through operator entry of a randomization variable obtained from IWRS at the time of enrollment and randomization. This randomization variable (A or B), the meaning of which is blinded to the operator, is entered into the control box and determines the mode of the device as either active insonation or sham insonation.
Study Groups
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Control group (tPA + sham TUS)
Control group (tPA + sham TUS) During the primary phase of the study, subjects will be randomized 1:1
Group Type
SHAM_COMPARATOR
tPA in combination with the Sonolysis Headframe (Sham TUS)
Intervention Type
DEVICE
tPA per approved labeling Sham (inactive) TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes
Treatment group (tPA + TUS)
Treatment group (tPA + TUS): Lead-in phase and Primary phase
Group Type
ACTIVE_COMPARATOR
tPA in combination with the Sonolysis Headframe (TUS)
Intervention Type
DEVICE
tPA: 60 minutes per approved labeling TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes
Interventions
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tPA in combination with the Sonolysis Headframe (TUS)
tPA: 60 minutes per approved labeling TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes
Intervention Type
DEVICE
tPA in combination with the Sonolysis Headframe (Sham TUS)
tPA per approved labeling Sham (inactive) TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes
Intervention Type
DEVICE
Other Intervention Names
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Aureva Headframe (TUS) with Tissue Plaminogen Activator (tPA)
Aureva Headframe (Sham TUS) with Tissue Plaminogen Activator (tPA)
Eligibility Criteria
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Inclusion Criteria
1. Subjects with acute ischemic stroke
2. Subjects that initially present at non-EVT treating hospitals that have established transport services in place to transfer subjects to hospitals capable of performing EVT
3. Males or females 18 - 80 years of age
4. Subjects presenting within time window for IV tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms
5. No signs of intracranial bleeding on assessment by non-contrast CT
6. Subjects that in the opinion of the treating physician require treatment with full dose of IV tPA (0.9mg/kg) as standard of care per institutional standards
7. SBP ≤ 185 mmHg and DBP ≤ 105 mmHg at baseline or after treatment of hypertension with medications prior to tPA bolus
8. Pre-morbid mRS of 0-1
9. Arterial occlusion in the middle cerebral artery (MCA) M1 or proximal M2, intracranial carotid T, anterior cerebral artery (ACA) A1, basilar, proximal posterior cerebral artery (PCA) P1 or intracranial tandem lesions in these locations visible on CT angiography (CTA)
10. Provision of informed consent as demonstrated by the subject's signature or by the signature of the subject's authorized legal representative on the Informed Consent Form in accordance with all local and national regulations and no later than 15 minutes after standard of care tPA administration
2. Subjects that initially present at non-EVT treating hospitals that have established transport services in place to transfer subjects to hospitals capable of performing EVT
3. Males or females 18 - 80 years of age
4. Subjects presenting within time window for IV tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms
5. No signs of intracranial bleeding on assessment by non-contrast CT
6. Subjects that in the opinion of the treating physician require treatment with full dose of IV tPA (0.9mg/kg) as standard of care per institutional standards
7. SBP ≤ 185 mmHg and DBP ≤ 105 mmHg at baseline or after treatment of hypertension with medications prior to tPA bolus
8. Pre-morbid mRS of 0-1
9. Arterial occlusion in the middle cerebral artery (MCA) M1 or proximal M2, intracranial carotid T, anterior cerebral artery (ACA) A1, basilar, proximal posterior cerebral artery (PCA) P1 or intracranial tandem lesions in these locations visible on CT angiography (CTA)
10. Provision of informed consent as demonstrated by the subject's signature or by the signature of the subject's authorized legal representative on the Informed Consent Form in accordance with all local and national regulations and no later than 15 minutes after standard of care tPA administration
Exclusion Criteria
1. Tandem lesions where one lesion is extracranial (carotid or vertebral artery)
2. ASPECTS score \< 6 on non contrast CT or ischemic changes that in the opinion of the investigator would be medically inappropriate for reperfusion therapy
3. Poor collateral circulation defined as minimal or no pial collaterals in \>50% of the ischemic territory
4. Expected time between activation of Sonolysis Headframe and initiation of EVT \< 90 minutes
5. Pregnant or breast feeding women, clinical signs of pericarditis, sepsis or any other serious medical illness likely to interact with treatment, confounding preexistent neurological or psychiatric disease or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study
6. Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2
7. No permanent address or phone number
8. Any investigational drug \<14 days prior to study participation
9. Subjects with known allergy to x-ray contrast material
10. Subjects with any standard contraindication for intravenous tPA therapy as per local or national guidelines
2. ASPECTS score \< 6 on non contrast CT or ischemic changes that in the opinion of the investigator would be medically inappropriate for reperfusion therapy
3. Poor collateral circulation defined as minimal or no pial collaterals in \>50% of the ischemic territory
4. Expected time between activation of Sonolysis Headframe and initiation of EVT \< 90 minutes
5. Pregnant or breast feeding women, clinical signs of pericarditis, sepsis or any other serious medical illness likely to interact with treatment, confounding preexistent neurological or psychiatric disease or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study
6. Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2
7. No permanent address or phone number
8. Any investigational drug \<14 days prior to study participation
9. Subjects with known allergy to x-ray contrast material
10. Subjects with any standard contraindication for intravenous tPA therapy as per local or national guidelines
Minimum Eligible Age
18 Years
Maximum Eligible Age
80 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Cerevast Medical, Inc.
INDUSTRY
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Andrei V Alexandrov, MD
Role: PRINCIPAL_INVESTIGATOR
University of Tennessee
Locations
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The University of Tennessee Health Science Center
Memphis, Tennessee, United States
Site Status
Memorial Hermann Hospital - Texas Medical Center (TMC)
Houston, Texas, United States
Site Status
Countries
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United States
References
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Writing Group Members; Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016 Jan 26;133(4):e38-360. doi: 10.1161/CIR.0000000000000350. Epub 2015 Dec 16. No abstract available.
Reference Type
BACKGROUND
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
Reference Type
BACKGROUND
Zivin JA. Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA). Ann Neurol. 2009 Jul;66(1):6-10. doi: 10.1002/ana.21750.
Reference Type
BACKGROUND
Gravanis I, Tsirka SE. Tissue-type plasminogen activator as a therapeutic target in stroke. Expert Opin Ther Targets. 2008 Feb;12(2):159-70. doi: 10.1517/14728222.12.2.159.
Reference Type
BACKGROUND
Mishra SM, Dykeman J, Sajobi TT, Trivedi A, Almekhlafi M, Sohn SI, Bal S, Qazi E, Calleja A, Eesa M, Goyal M, Demchuk AM, Menon BK. Early reperfusion rates with IV tPA are determined by CTA clot characteristics. AJNR Am J Neuroradiol. 2014 Dec;35(12):2265-72. doi: 10.3174/ajnr.A4048. Epub 2014 Jul 24.
Reference Type
BACKGROUND
Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P, Watson T, Goyal M, Demchuk AM. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010 Oct;41(10):2254-8. doi: 10.1161/STROKEAHA.110.592535. Epub 2010 Sep 9.
Reference Type
BACKGROUND
Raychev R, Saver JL. Mechanical thrombectomy devices for treatment of stroke. Neurol Clin Pract. 2012 Sep;2(3):231-235. doi: 10.1212/CPJ.0b013e31826af206.
Reference Type
BACKGROUND
Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7;368(10):893-903. doi: 10.1056/NEJMoa1214300. Epub 2013 Feb 7.
Reference Type
BACKGROUND
Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013 Mar 7;368(10):914-23. doi: 10.1056/NEJMoa1212793. Epub 2013 Feb 8.
Reference Type
BACKGROUND
Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013 Mar 7;368(10):904-13. doi: 10.1056/NEJMoa1213701. Epub 2013 Feb 6.
Reference Type
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.
Reference Type
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.
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.
Reference Type
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, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
Reference Type
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.
Reference Type
BACKGROUND
Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moye LA, Hill MD, Wojner AW; CLOTBUST Investigators. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004 Nov 18;351(21):2170-8. doi: 10.1056/NEJMoa041175.
Reference Type
BACKGROUND
Tsivgoulis G, Eggers J, Ribo M, Perren F, Saqqur M, Rubiera M, Sergentanis TN, Vadikolias K, Larrue V, Molina CA, Alexandrov AV. Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke. 2010 Feb;41(2):280-7. doi: 10.1161/STROKEAHA.109.563304. Epub 2009 Dec 31.
Reference Type
BACKGROUND
Sakharov DV, Rijken DC. The effect of flow on lysis of plasma clots in a plasma environment. Thromb Haemost. 2000 Mar;83(3):469-74.
Reference Type
BACKGROUND
Guo T, Li H, Lv Y, Lu H, Niu J, Sun J, Yang GY, Ren C, Tong S. Pulsed Transcranial Ultrasound Stimulation Immediately After The Ischemic Brain Injury is Neuroprotective. IEEE Trans Biomed Eng. 2015 Oct;62(10):2352-7. doi: 10.1109/TBME.2015.2427339. Epub 2015 Apr 28.
Reference Type
BACKGROUND
Alexandrov AV, Barlinn K, Strong R, Alexandrov AW, Aronowski J. Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats. Transl Stroke Res. 2011 Sep;2(3):376-81. doi: 10.1007/s12975-011-0080-6. Epub 2011 Apr 21.
Reference Type
BACKGROUND
Barreto AD, Alexandrov AV, Shen L, Sisson A, Bursaw AW, Sahota P, Peng H, Ardjomand-Hessabi M, Pandurengan R, Rahbar MH, Barlinn K, Indupuru H, Gonzales NR, Savitz SI, Grotta JC. CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke. 2013 Dec;44(12):3376-81. doi: 10.1161/STROKEAHA.113.002713. Epub 2013 Oct 24.
Reference Type
BACKGROUND
Khatri P, Neff J, Broderick JP, Khoury JC, Carrozzella J, Tomsick T; IMS-I Investigators. Revascularization end points in stroke interventional trials: recanalization versus reperfusion in IMS-I. Stroke. 2005 Nov;36(11):2400-3. doi: 10.1161/01.STR.0000185698.45720.58. Epub 2005 Oct 13.
Reference Type
BACKGROUND
Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, Marks MP, Prabhakaran S, Kallmes DF, Fitzsimmons BF, Mocco J, Wardlaw JM, Barnwell SL, Jovin TG, Linfante I, Siddiqui AH, Alexander MJ, Hirsch JA, Wintermark M, Albers G, Woo HH, Heck DV, Lev M, Aviv R, Hacke W, Warach S, Broderick J, Derdeyn CP, Furlan A, Nogueira RG, Yavagal DR, Goyal M, Demchuk AM, Bendszus M, Liebeskind DS; Cerebral Angiographic Revascularization Grading (CARG) Collaborators; STIR Revascularization working group; STIR Thrombolysis in Cerebral Infarction (TICI) Task Force. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke. 2013 Sep;44(9):2650-63. doi: 10.1161/STROKEAHA.113.001972. Epub 2013 Aug 6. No abstract available.
Reference Type
BACKGROUND
Jung C, Yoon W, Ahn SJ, Choi BS, Kim JH, Suh SH. The Revascularization Scales Dilemma: Is It Right to Apply the Treatment in Cerebral Ischemia Scale in Posterior Circulation Stroke? AJNR Am J Neuroradiol. 2016 Feb;37(2):285-9. doi: 10.3174/ajnr.A4529. Epub 2015 Sep 17.
Reference Type
BACKGROUND
Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, Sacks D; Technology Assessment Committee of the American Society of Interventional and Therapeutic Neuroradiology; Technology Assessment Committee of the Society of Interventional Radiology. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003 Aug;34(8):e109-37. doi: 10.1161/01.STR.0000082721.62796.09. Epub 2003 Jul 17.
Reference Type
BACKGROUND
Other Identifiers
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CM-CP-01
Identifier Type: -
Identifier Source: org_study_id