Therapeutic Advances in Neurological Disorders has published “Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke”. This paper presents a case study of the CLOTBUST-ER trial, showing that the “increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies “. With the rise of EVT during the course of the trial, the segment of the eligible stroke population who were most likely to receive the best outcomes from sonothrombolysis were disproportionately redirected away from the trial. The paper includes a post hoc analysis suggesting that this shift negatively impacted the CLOTBUST-ER results. This analysis reinforces the importance of the improvements that Cerevast is implementing in the phase 3 TRUST study.
Under a development and commercial supply agreement, Lantheus’ microbubble will be used in combination with Cerevast’s ocular ultrasound device to target improving blood flow in occluded retinal veins in the eye. Cerevast’s RVO Technology will combine intravenous administration of Lantheus’ microbubbles with non-invasive ultrasound delivered across the closed eyelid. By treating the underlying cause of the disease as opposed to the symptoms, this therapy has the potential to reduce or eliminate the need for chronic maintenance therapy and improve the quality of life for those patients inflicted by RVO. Cerevast’s RVO Technology is expected to enter a Phase 2B clinical trial in the second half of 2019. Cerevast has received an investigational device exemption (IDE) from the U.S. FDA, which allows its investigational ocular ultrasound device to be used in a clinical study in order to collect safety and effectiveness data. If approved, the RVO Technology could be commercialized in 2023.
The results of the CLOTBUST-ER trial, the first phase 3 trial to assess the safety and efficacy of sonothrombolysis, have been published in the April 2019 edition of Lancet Neurology. Though the trial did not meet its primary endpoint, the article and accompanying independent commentary offer a cogent review of the obstacles and shortcomings which may have impaired the CLOTBUST-ER trial, and highlights the continued promise of sonothrombolysis as a safe and effective option for acute ischemic stroke treatment. The publication also introduces the Cerevast Medical sponsored phase 3 TRUST study as an opportunity to incorporate the lessons learned from CLOTBUST-ER and unlock the potential of sonothrombolysis to advance the standard of care.
By Kevin King (Southeast Texas Vital Signs, Fall 2018)
Baptist Hospital in Beaumont has been chosen as the initial site for a clinical study involving its stroke patients. The TRUST study is sponsored and monitored by Cerevast, a medical technology company from Washington State that develops medical devices for acute ischemic stroke.
“This is a very proud moment and it’s a good thing for our community,” said Kellie DeMary, administrative director of Emergency Services at Baptist Hospital in Beaumont. “This will help us to take care of these patients even better.”
Cerevast, Dr. Andrew D. Barreto at Memorial Hermann – Texas Medical Center (TMC) in Houston and other medical professionals involved in the study will evaluate the Aureva Pulse as a therapy for Baptist’s stroke patients, who do not have immediate access to mechanical thrombectomy and must undergo lengthy transport times to receive this treatment at Hermann Memorial hospitals in Houston. These patients are usually transported by air medical services to receive a mechanical thrombectomy.
Ischemic strokes happen when a blood clot (thrombus) or a fatty deposit blocks an artery supplying blood to the brain. Mechanical thrombectomy is a procedure in which a long catheter is used to physically break up the clot. This represents a newer device-based approach to treating ischemic stroke that has been shown to be highly effective at removing large vessel occlusions. How-ever, because this procedure re-quires specialized facilities and trained medical staff, the majority of mechanical thrombectomy cases performed in the United States are limited to a small percentage of primary stroke centers and approximately 125 Joint Commission certified comprehensive stroke centers, such as TMC in Houston.
Stroke patients are frequently admitted to outlying community-based hospitals without the required facilities or capabilities to perform mechanical thrombectomy, forcing transport to a comprehensive or primary stroke center following the initial diagnosis and initiation of tissue plasminogen activator (tPA), clot-busting agent used in the treatment of heart attack and stroke. These transfers often involve significant time delays during which brain tissue remains deprived of oxygen.
Since being approved by the U.S. Food and Drug Administration in 1996, tPA remains the only approved drug in the United States for the treatment of ischemic stroke, according to an article pub-lished in the U.S. National Library of Medicine National Institutes of Health. Although tPA is generally effective at dissolving smaller blood clots, it is only effective at dissolving larger proximal vessel occlusions in 15-25 percent of all cases, several studies have shown.
Barreto said a previous study published in the New England Journal of Medicine found that using ultra-sonic waves, like those the Aureva Pulse uses, along with tPA tripled the effectiveness of dis-solving blood clots in stroke patients.
“The ultrasound helps tPA work better, or the ultra-sound may vibrate the clot and break it up better than tPA alone,” Barreto said.
By breaking up these clots in a more effective manner, strokes could be smaller and patients could have less disability.
“It could save lives or reduce disability,” Barreto said.
Cerevast claims the Aureva Pulse, a device that is placed on the head almost like a king’s crown, represents a first-in-class stroke treatment device designed to address this treatment gap.
“Used in combination with tPA during the acute phase of ischemic stroke to help Baptist Hospital chosen as initial site for study that may have global implications, impact future of treating stroke patients break-up blood clots and restore blood flows to the ischemic regions of the brain, the device consists of the ultrasonic head-frame that properly orients the ultrasound transducer into the proper location on the patient’s head and a control box that gen-erates the ultrasound signal and provides the user interface controls,” a release by the company states.
According to Cerevast, features of the device enable the ultrasound to be directed to the target region of the brain without the need for a trained ultrasound technician to deliver the therapy. Based on the portable nature of the device, therapy can be administered while stroke patients are undergoing transport via ambulance or helicopter to a primary or comprehensive stroke center to receive thrombectomy.
Baptist is one of around 20 U.S. medical facilities whose patients may consent to the study. If successful in the United States, the study will be expanded to more than 70 medical facilities world-wide likely in Europe, Eastern Asia, and South America, said Joyce Su, director of Clinical Affairs for Cerevast.
Beaumont is one of the “spoke” hospitals in the southeast Texas region that feed into the hub at Memorial Hermann – Tex-as Medical Center (TMC) in Houston, Su said. “One of the region’s leading stroke neurologists, Dr. Andrew D. Barreto at TMC, is an outspoken proponent of using ultrasound to enhance the clotbusting effect of tPA for stroke. Dr. Barreto provides telemedicine neurology services to many outlying hospitals in Southeast Texas, including Baptist (in) Beaumont. Dr. Barreto wanted TMC to be a part of the TRUST trial and he specifically requested that Baptist Beaumont be the first spoke site in the trial, which they have graciously accepted to agree to participate.”
The hospital hosted a presentation by Cerevast to introduce and train medical staff to use the Aureva Pulse and to educate staff on the study and what their role and the role of patients who agree (possibly through family members who are legally designated to make medical decisions for them on-site) to participate in the study.
“Cerevast Medical is exceedingly pleased that Baptist Beaumont, Hermann Memorial TMC and Dr. Barreto have agreed to work on the study,” said John Alleman, Chief Operations Officer at Cerevast. “We simply could not ask for a better group of professionals to work with. We believe that this therapy can provide a substantial life-saving benefit to stroke patients and we are lucky to have a champion like Dr. Barreto.”
Su also wanted to stress that Dr. Barre-to has no financial ties to Cerevast Medical nor has derived any financial benefit in assisting with the study.
Cerevast hopes to have the lead-in phase of the study completed in early 2019 and then complete the subsequent primary phase in late 2020.
Redmond, WA and Tempe, AZ USA — Cerevast Medical, Inc., a medical technology company that develops medical products for the treatment of neurologic disorders, has licensed several technologies from Arizona State University to be used in innovative post-stroke rehabilitation devices. The technologies were developed by Dr. Jamie Tyler in the School of Biological and Health Systems Engineering, one of the Ira A. Fulton Schools of Engineering at ASU.
“Dr. Tyler is a recognized leader in the field of modulating cellular activity using ultrasound,” said Bradford Zakes, Cerevast president and CEO. “These technologies augment our existing IP portfolio and will enable the development of sophisticated, non-invasive new therapies for post-stroke brain rehabilitation.”
The CDC reports nearly 800,000 stroke victims in the United States each year. The vast majority of stroke victims survive, but with injuries to the brain that can severely impact their ability to work or care for themselves.
Transcranial Ultrasound (TUS) Therapy transmits ultrasonic energy into the motor cortex region of the brain to promote recovery and rehabilitation following a stroke. When used in combination with traditional physical therapy, TUS increases neuroplasticity, making it easier for the brain to route new pathways to regain physical movements.
Unlike competing therapies that required the surgical implantation of electrodes, TUS can be performed non-invasively. It also reaches deeper regions of the brain than other non-invasive technologies like transcranial magnetic stimulation. In addition, TUS is the only non-invasive brain stimulation technology to receive regulatory approval outside the U.S. for post-stroke recovery.
“The field of neuromodulation—which has now drawn extensive interest from federal funding agencies and other labs—really began moving again through the work done at ASU,” said Dr. Tyler. “This is an area of medicine that has tremendous potential for treating a wide range of neurologic disorders and I am very pleased to see a company with the accomplishments of Cerevast using these technologies.”
The license was completed through Arizona Technology Enterprises (AzTE), the exclusive intellectual property management and technology transfer organization of Arizona State University.
About Cerevast Medical
Cerevast Medical, Inc. is a late-stage medical technology company focused on the development of TUS for the treatment of acute ischemic stroke and post-stroke rehabilitation. Cerevast is a recognized leader in the field of TUS with a dominant intellectual property estate comprising more than 75 issued patents. The Company is a privately held corporation based in Redmond, Washington. For more information, visit http://www.cerevast.com.
About Arizona Technology Enterprises (AzTE)
AzTE is a non-profit organization that operates as the exclusive intellectual property management and technology transfer organization for ASU and its research enterprise. Comprising industry and university veterans, AzTE brings together ASU’s researchers and industry partners to transform discoveries into marketable products and services, taking innovation out of the lab and into the commercial marketplace. Nearly 100 companies have been launched based on ASU technologies. AzTE currently offers for licensing more than 300 novel technologies in the life and physical sciences. For more information: http://www.azte.com.