The use of an ultrasound device along with tissue plasminogen activator (tPA) is safe, based on the results of a phase II trial published online Oct. 24 in Stroke.
The CLOTBUST-HF (Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free) safety trial included 20 participants who had an ischemic stroke. The device uses 2-MHz ultrasound waves and does not exceed approved exposure levels.
“If found to be safe, a simple-to-apply HF [hands-free] device would facilitate a large-scale, phase III sonothrombolysis trial in patients with acute ischemic stroke,” wrote the authors, led by Andrew D. Barreto, MD, of the University of Texas Health Science Center at Houston.
Participating patients who had an intracranial blockage received intravenous tPA 4.5 hours or earlier from the time the patient last appeared neurologically normal. Most had middle cerebral artery occlusions. After the tPA bolus, patients wore the device, which delivered two hours of exposure to 2-MHz pulse-wave ultrasound. Symptomatic intracerebral hemorrhage was the primary outcome.
Patients received a transcranial Doppler or a CT angiogram both before and after treatment. Researchers calculated National Institutes of Health Stroke Scale scores at two hours and a modified Rankin scale at 90 days.
During the study period between October 2010 and September 2011, no patients experienced a symptomatic intracerebral hemorrhage and there were no adverse events related to the device. Complete recanalization after two hours occurred in 40 percent of patients and partial recanalization occurred in 10 percent of patients. At 90 days, Rankin scale scores were between 0 and 1.
The authors acknowledged the study’s small sample size, but argued that previous study findings augment the validity of their results about the safety of this type of device.
“The challenge with widespread sonothrombolysis 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,” the authors explained. “The HF device tested in this study represents a leap forward with regard to feasibility in executing a large phase III efficacy trial.”
A phase III trial, CLOTBUST-ER, is currently ongoing.
Cerevast Therapeutics provided the devices in the study.