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News from the International Stroke Conference: Hands-free Headband Device Improves Clotbuster Efficacy

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device is composed of 18 ultrasound probes, which are activated sequentially to provide therapeutic ultrasound to the Circle of Willis and the proximal branches including the posterior intracranial circulation vessels. A nosepiece guides placement of the head frame and plastic hooks attached behind the ears. A screw device allows the clinicians to racket the device until it fits on the head snugly. The frame connects to a battery-powered control box.

NEW ORLEANS—A hands-free device that can be placed and held into position on a stroke patient's head appears to improve the rate of opening blood vessels causing brain attacks, researchers said here at the American Stroke Association's International Stroke Conference.

The hands-free device called the Clotbust ER [Combined Lysis of Thrombus in Brain Ischemia with Transcranial Ultrasound and Systemic TPA] is composed of 18 ultrasound probes, which are activated sequentially to provide therapeutic ultrasound to the Circle of Willis and the proximal branches including the posterior intracranial circulation vessels.

In the pilot study, eight of 20 patients (40 percent) achieved complete target vessel recanalization when they were fitted with the headband, which was activated for two hours, and administered tissue plasminogen activator (tPA), Andrew D. Barreto, MD, assistant professor of neurology at the University of Texas Medical School in Houston, reported.

“That compares favorably with the original study of the hands-held device in which 38 percent of patient achieved recanalization,” he told Neurology Today at his presentation. Historically, the use of tPA alone results in a recanalization rate of about 15 percent, Dr. Barreto said.

In addition to the 40 percent success rate in completely opening the blocked brain arteries, he said that two other patients achieved a partial recanalization, improving the benefit rate to 50 percent of the patients in the phase 2 study.

The primary study outcome was safety — the investigators wanted to determine if the headband device caused symptomatic intracerebral hemorrhage. Prior to the current study, 15 healthy volunteers tolerated the procedure without any change on magnetic resonance permeability imaging. “In this study, all 20 patients tolerated the two-hour treatment,” Dr. Barreto said.

The study was closely monitored by an independent data and safety monitoring board and all serious adverse events (including deaths) were closely reviewed. Dr. Barreto and his colleagues reported that there were no symptomatic intracerebral hemorrhages and that no adverse events were attributed to the device. Overall mortality in the study was 20 percent — four people died. None of the deaths were determined to be related to the study device or study treatment. Rather, the patients died from complications related to their stroke. Five (25 percent) of the participants were discharged at 90 days with a favorable outcome — a score of 0 or 1 on the modified Rankin Scale.

Dr. Barreto explained at his poster presentation that the array of transponders in the headband device was positioned to cover all the areas of the skull so they could impact any of the areas where blockages occurred. “The ultrasound signal was strong enough to be picked up on the opposite side of the head,” he noted.

“We know through previous studies that the clots respond to ultrasound by expanding,” he said, illustrating the concept by intertwining his fingers into a tight two-handed fist and then relaxing and widening the fingers so that gaps occurred in the grasp. He said that when ultrasound hits the clot, the fibrin knots relax and open, allowing for better penetration of clotbusting drugs.

Previous studies have shown that focusing ultrasound on the clot and then administering tPA results in a better recanalization rate of the affected blood vessel, and in improved outcomes.

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reported that there were no symptomatic intracerebral hemorrhages and that no adverse events were attributed to the device.

He noted that his study, Combined Lysis of Thrombus in Brain Ischemia with Transcranial Ultrasound and Systemic TPA Hands-Free (CLOTBUST HF), is the first-NINDS-sponsored, multicenter, open label, pilot safety study of tPA plus a novel operator-independent ultrasound device in patients with ischemic stroke due to proximal intracranial occlusion.

EXPERTS COMMENT

“This is really an exciting development,” commented L. Dana DeWitt, MD, professor of neurology and medical director of the inpatient Neurology/Neurosurgery Service at the University of Utah in Salt Lake City, who was not involved with the study. “We have a small stroke unit and there are times when we do not have the staff to hold a transponder in place for two hours.”

Dr. DeWitt said she was impressed by the initial findings of the study and looked forward to the data from the planned, expanded phase 3 trial of the device.

Dr. Barreto said that the phase 3 trial will randomly assign stroke patients — the goal is to enroll 800 — to the operating device or a dummy. The battery pack of the control device will drain as if it is being utilized, which will prevent the clinician from knowing whether the patients is on an activated or placebo arm of the trial.

Cerevast Therapeutics of Redmond, WA, is sponsoring the phase 3 trial.

MORE ON THE STUDY PROTOCOLS

  • Patients were included in the pilot study if they were diagnosed with a disabling focal neurological deficit. They received intravenous recombinant-tPA in a dose of 0.9 mg/kg as a 10% bolus and 90% infusion over one hour with a maximum dose of 90 mg administered. They had to undergo the tPA treatment within 4.5 hours after the onset of symptoms. The patients were also required to have been diagnosed through transcranial Doppler as having an intracranial occlusion of the middle cerebral artery, anterior cerebral artery, internal carotid artery, posterior cerebral artery, vertebral or distal basilar artery.
  • All patients underwent pre- and post-treatment assessment of vascular patency and recanalization measured by standardized transcranial Doppler or computer-assisted tomography angiography criteria. NIH Stroke Scale scores were collected at two-hours and modified Rankin Scores at 90 days.
  • The clot causing the stroke was located in the middle cerebral artery in 14 of the patients; 8 of those arteries were completely opened within the 24-hour time frame of the trial.
  • Exclusion criteria were use of intra-arterial tPA and contraindications for tPA use including an NIHSS score greater than 25; the combination of a previous stroke and diabetes; and age greater than 80 years.