CLOTBUST-Hands Free: Pilot Safety Study of a Novel Operator-Independent Ultrasound Device in Patients With Acute Ischemic Stroke

• Published in: Stroke (1970) Vol. 44; no. 12; pp. 3376 - 3381
• Main Authors: Barreto, Andrew D., Alexandrov, Andrei V., Shen, Loren, Sisson, April, Bursaw, Andrew W., Sahota, Preeti, Peng, Hui, Ardjomand-Hessabi, Manouchehr, Pandurengan, Renganayaki, Rahbar, Mohammad H., Barlinn, Kristian, Indupuru, Hari, Gonzales, Nicole R., Savitz, Sean I., Grotta, James C.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.12.2013; Lippincott Williams & Wilkins
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Brain Ischemia - diagnostic imaging; Brain Ischemia - drug therapy; Brain Ischemia - therapy; Combined Modality Therapy; Female; Fibrinolytic Agents - therapeutic use; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Pilot Projects; Prospective Studies; Stroke - diagnostic imaging; Stroke - drug therapy; Stroke - therapy; Thrombolytic Therapy - adverse effects; Thrombolytic Therapy - instrumentation; Tissue Plasminogen Activator - therapeutic use; Treatment Outcome; Ultrasonography, Doppler, Transcranial - adverse effects; Ultrasonography, Doppler, Transcranial - instrumentation; Vascular diseases and vascular malformations of the nervous system; Sonography; Doppler ultrasound study; Human; Cerebral infarction; sonothrombolysis; Stroke; Nervous system diseases; Cardiovascular disease; Cerebral disorder; ultrasonography, doppler, transcranial; Vascular disease; operator-independent device; Reperfusion; Treatment; CLOTBUST; Central nervous system disease; Brain ischemia; thrombolytic therapy; Ultrasound; Cerebrovascular disease; reperfusion; stroke
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/STROKEAHA.113.002713

BACKGROUND AND PURPOSE—The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health–sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion. METHODS—All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days. RESULTS—Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5–29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows8 of 20 (40%; 95% confidence interval, 19%–64%) complete and 2 of 20 (10%; 95% confidence interval, 1%–32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate8 of 14 (57%; 95% confidence interval, 29%–82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%–49) patients had a modified Rankin scale of 0 to 1. CONCLUSIONS—Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial. CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierCLOTBUST-HF NCT01240356.