CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke.

Abstract

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 follows: 14 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 follows: 8 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 rate: 8 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 URL:

http://www.clinicaltrials.gov. Unique identifier: CLOTBUST-HF NCT01240356.

• Authors: Andrew D Barreto, Andrei V Alexandrov, Loren Shen, April Sisson, Andrew W Bursaw, Preeti Sahota, Hui Peng, Manouchehr Ardjomand-Hessabi, Renganayaki Pandurengan, Mohammad H Rahbar, Kristian Barlinn, Hari Indupuru, Nicole R Gonzales, Sean I Savitz, James C Grotta
• Journal: Stroke (Stroke) Vol. 44 Issue 12 Pg. 3376-81 (Dec 2013) ISSN: 1524-4628 [Electronic] United States
• PMID: 24159060 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Fibrinolytic Agents
• Tissue Plasminogen Activator

Topics

• Aged
• Aged, 80 and over
• Brain Ischemia (diagnostic imaging, drug therapy, therapy)
• Combined Modality Therapy
• Female
• Fibrinolytic Agents (therapeutic use)
• Humans
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Stroke (diagnostic imaging, drug therapy, therapy)
• Thrombolytic Therapy (adverse effects, instrumentation)
• Tissue Plasminogen Activator (therapeutic use)
• Treatment Outcome
• Ultrasonography, Doppler, Transcranial (adverse effects, instrumentation)