Novel Ultrasound Device Plus tPA Appears Safe for Acute Ischemic Stroke

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Thrombolysis with low-power ultrasound energy delivered by a novel operator-independent device in addition to systemic tissue-type plasminogen activator (tPA) appears safe in patients with acute ischemic stroke, according to a pilot study published online October 24, 2013, ahead of print in Stroke. The combination strategy also shows hints of efficacy.

For the phase II CLOTBUST-HF (Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free) trial, Andrew D. Barreto, MD, of the University of Texas Health Science Center at Houston (Houston, TX), and colleagues enrolled 20 patients (60% men) with acute ischemic stroke at 2 centers. All patients received standard-dose IV tPA (0.9 mg/kg) within 4.5 hours of neurological normalcy and were exposed to 2 hours of 2-MHz transcranial Doppler ultrasound energy delivered by a novel operator-independent device (ClotBust-ER; Cerevast Therapeutics, Redmond, WA).

The median baseline National Institutes of Health (NIH) Stroke Scale score was 15 and the median time to tPA at the beginning of sonothrombolysis was 22 minutes. Pretreatment occlusion sites were:

• Middle cerebral artery: 70%
• Terminal internal carotid artery: 15%
• Vertebral artery: 15%

All patients tolerated 2 hours of treatment and none developed symptomatic intracranial hemorrhage. There were no serious adverse events related to the device.

At 2 hours, recanalization, assessed by transcranial Doppler or CTA imaging, was complete in 8 patients (40%; 95% CI 19-64%) and partial in 2 (10%; 95% CI 1-32%). Complete recanalization was greatest in middle cerebral artery occlusions (57%; 95% CI 29-82%).

At discharge, 13 patients (65%) went home or to acute rehabilitation; 3 (15%) had died. At 90 days, 1 additional patient had died and one-quarter of patients had a modified Rankin score of 0 or 1. Overall, a higher proportion of patients with vs. without complete recanalization exhibited a modified Rankin score of 0 or 1 at day 90 (60% vs. 38%; P = 0.299).

Widespread Use Now Possible

“[Hands-free] delivery of transcranial sonothrombolysis in combination with IV-tPA, seems potentially safe in patients with proximal intracranial arterial occlusions and may produce more complete recanalization compared with tPA alone,” Dr. Barreto and colleagues write. “Further study of this treatment combination seems warranted and is ongoing in a phase III efficacy trial.”

The challenge with widespread implementation “has been a lack of adequately trained sonographers who can quickly locate the intracranial thrombus and maintain a single, handheld transducer focused on the target,” they observe. But the ClotBust-ER device “represents a leap forward with regard to feasibility. . . . Using easily identified anatomic landmarks (eg, the pinna, bridge of nose, and occipital protuberance), medical professionals without neurosonology training will be able to place the device quickly in an emergent setting.”

 

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Source:
Barreto AD, Alexandrov AV, Shen L, et al. CLOTBUST-Hands Free: Pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke. 2013;Epub ahead of print.

 

 

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