Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): Design and methodology of a multinational phase 3 trial

International Journal of Stroke

Volumn 10, Issue 7, 2015, Pages 1141-1148

  Schellinger, Peter D ^a   Alexandrov, Andrei V ^b   Barreto, Andrew D ^c   Demchuk, Andrew M ^d   Tsivgoulis, Georgios ^b,e   Kohrmann, Martin ^f   Alleman, John ^g   Howard, Virginia ^h   Howard, George ^h   Alexandrov, Anne W ^b   Brandt, Gordon ^g   Molina, Carlos A ⁱ  

^a KLINIKUM MINDEN   (Germany)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^c UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF CALGARY   (Canada)

^e NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

^f UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^g Cerevast Therapeutics Inc   (United States)

^h UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

ⁱ HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

Author keywords

Acute stroke therapy; Clinical trial; Fibrinolysis; Rt PA; Sonolysis; Thrombolysis; Ultrasound

Indexed keywords

ALTEPLASE; PLACEBO; FIBRINOLYTIC AGENT; TISSUE PLASMINOGEN ACTIVATOR;

ARTICLE; BLOOD CLOT LYSIS; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CEREBRAL REVASCULARIZATION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; HUMAN; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; RANKIN SCALE; SYSTEMIC THERAPY; THERAPY EFFECT; TREATMENT OUTCOME; ULTRASOUND THERAPY; ADOLESCENT; ADULT; AGED; CLINICAL TRIAL; COMPLICATION; FEMALE; MALE; MIDDLE AGED; NONPARAMETRIC TEST; PROCEDURES; SEVERITY OF ILLNESS INDEX; STATISTICAL MODEL; STROKE; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BRAIN ISCHEMIA; DOUBLE-BLIND METHOD; FEMALE; FIBRINOLYTIC AGENTS; HUMANS; LOGISTIC MODELS; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; SEVERITY OF ILLNESS INDEX; STATISTICS, NONPARAMETRIC; STROKE; TISSUE PLASMINOGEN ACTIVATOR; TREATMENT OUTCOME; ULTRASONIC THERAPY; YOUNG ADULT;

EID: 84942296313     PISSN: 17474930     EISSN: 17474949     Source Type: Journal    
DOI: 10.1111/ijs.12536     Document Type: Article

References (29)

1. The NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333:1581-1587.
2. Hacke W, Kaste M, Bluhmki E etal. Thrombolysis with alteplase 3 to 4·5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317-1329.
3. Alexandrov AV, Burgin WS, Demchuk AM, El-Mitwalli A, Grotta JC. Speed of intracranial clot lysis with intravenous TPA therapy: sonographic classification and short term improvement. Circulation 2001; 103:2897-2902.
4. Fischer U, Arnold M, Nedeltchev K etal. NIHSS score and arteriographic findings in acute ischemic stroke. Stroke 2005; 36:2121-2125.
5. Saqqur M, Uchino K, Demchuk AM etal. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 2007; 38:948-954.
6. Francis CW, Blinc A, Lee S, Cox C. Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol 1995; 21:419-424.
7. Lauer CG, Burge R, Tang DB, Bass BG, Gomez ER, Alving BM. Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis. Circulation 1992; 86:1257-1264.
8. Tsivgoulis G, Culp WC, Alexandrov AV. Ultrasound enhanced thrombolysis in acute arterial ischemia. Ultrasonics 2008; 48:303-311. doi: 10.1016/j.ultras.2007.11.008; Epub 2007 Dec 15. Review. PubMed PMID: 18511094.
9. Tsivgoulis G, Alexandrov AV. Ultrasound-enhanced thrombolysis in acute ischemic stroke: potential, failures, and safety. Neurother 2007; 4:420-427. Review. PubMed PMID: 17599707.
10. Polak JF. Ultrasound energy and the dissolution of thrombus. N Engl J Med 2004; 351:2154-2155.
11. Alexandrov AV, Barlinn K, Strong R, Alexandrov AW, Aronowski J. Low-power 2MHz pulsed-wave transcranial Doppler reduces ischemic brain damage in rat. Transl Stroke Res 2011; 2:376-381.
12. Alexandrov AV, Molina CA, Grotta JC etal. Wojner AW for the CLOTBUST Investigators. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004; 351:2170-2178.
13. Tsivgoulis G, Eggers J, Ribo M etal. Safety, efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke 2010; 41:280-287.
14. Ricci S, Dinia L, Del Sette M etal. Sonothrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2012; (10):CD008348.
15. Barlinn K, Tsivgoulis G, Barreto AD etal. Outcomes following sonothrombolysis in severe acute ischemic stroke: subgroup analysis of the CLOTBUST trial. Int J Stroke 2014; 9:1006-1010.
16. Barlinn K, Barreto AD, Sisson A etal. CLOTBUST-Hands Free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers. Stroke 2013; 44:1641-1646.
17. Barreto AD, Alexandrov AV, Shen L etal. CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke 2013; 44:3376-3381.
18. Zaidat OO, Yoo AJ, Khatri P, for the Cerebral Angiographic Revascularization Grading (CARG) Collaborators etal. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013; 44:2650-2663.
19. Linfante I, Llinas RH, Selim M etal. Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke 2002; 33:2066-2071.
20. Wahlgren N, Ahmed N, Dávalos A etal. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369:275-282.
21. Lees KR, Bath PM, Schellinger PD etal. Contemporary outcome measures in acute stroke research: choice of primary outcome measure. Stroke 2012; 43:1163-1170.
22. Bath PM, Lees KR, Schellinger PD etal. Statistical analysis of the primary outcome in acute stroke trials. Stroke 2012; 43:1171-1178.
23. Schellinger PD, Bath PM, Lees KR etal. Assessment of additional endpoints for trials in acute stroke - what, when, where, in who? Int J Stroke. 2012; 7:227-230.
24. Berkhemer OA, Fransen PS, Beumer D etal. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372:11-20.
25. Goyal M, Demchuk AM, Menon BK etal. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372:1019-1030.
26. Campbell BC, Mitchell PJ, Kleinig TJ etal. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372:1009-1018.
27. Howard G, Waller JL, Voeks JH etal. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke 2012; 43:664-669. PMID: 22343650.
28. Haršány M, Tsivgoulis G, Alexandrov AV. Intravenous thrombolysis in acute ischemic stroke: standard and potential future applications. Expert Rev Neurother 2014; 2:1-14.
29. Tsivgoulis G, Alleman J, Katsanos AH etal. Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit-risk analysis of clinical trials. Brain Behav. 2014; 4:789-797.