Cerevast Therapeutics Inc., a privately-held medical technology company, has started patient enrollment in its phase III clinical trial evaluating the use of the company’s proprietary Clotbust ER ultrasonic headframe for the treatment of acute ischemic stroke. This worldwide study intends to enroll up to 800 ischemic stroke patients in a randomized, double-blinded clinical trial designed to evaluate the efficacy and safety of the Clotbust ER ultrasound device when used in combination with standard intravenous thrombolytic therapy (tissue plasminogen activator - tPA/Alteplase).

Clotbust ER is a first-in-class ultrasound device for the treatment of ischemic stroke, representing a novel product with the potential to serve as the most significant advancement in stroke care since tPA was approved in 1996. Designed for rapid deployment in the emergency room setting, the device has been engineered to non-invasively deliver therapeutic ultrasound energy to the region of the occluded vessel in the brain.

Clinical data from five independent studies has demonstrated that combining the acoustic energy of ultrasound with conventional intravenous (IV) tPA therapy dissolves blood clots more completely and provides patients with better long term clinical outcomes compared to IV tPA therapy alone. Based on the results of these studies, the Clotbust ER received European CE mark clearance in December 2011.

“Initiation of the CLOTBUST ER phase III study represents a significant milestone for Cerevast,” said Bradford A Zakes, chief executive officer. “Clinical data in over 200 subjects has demonstrated that the addition of transcranial ultrasound to conventional IV tPA therapy has a favorable safety profile and results in significant improvements in vessel recanalization and 90-day clinical outcomes in ischemic stroke patients when compared to IV tPA therapy alone. We believe that this phase III clinical study will further demonstrate the therapeutic potential of this proprietary technology as we continue to advance the Clotbust ER ultrasound device towards commercial approval in the US.”

The CLOTBUST ER phase III clinical study is being conducted at over 60 leading stroke centres in 14 countries worldwide. The trial will enroll ischemic stroke patients with baseline National Institute of Health Stroke Scale (NIHSS) scores of 10 or greater. Patients will be randomized (400 per arm) to either Clotbust ER ultrasound in combination with IV tPA therapy  or standard IV tPA therapy alone. The primary endpoint of the study is 90-day functional outcome as measured by the percentage of patients that achieve a modified Rankin (mRS) score of 0-1 at 90 days post-treatment. The study will also evaluate complete vessel recanalization as a secondary endpoint in a subset of patients that undergo pre and post-treatment MRI or CT angiography. Two interim analyses are scheduled to be performed by the study’s Data Safety Monitoring Board (DSMB) upon completion of one-third and two-thirds of enrollment.

“The body of clinical evidence demonstrating the clinical utility of transcranial ultrasound as a means of effectively augmenting conventional IV thrombolysis therapy for the treatment of acute ischemic stroke has been steadily increasing over the past several years,” said Andrei Alexandrov, MD, Professor of Neurology, director, UAB Comprehensive Stroke Research Center and Global PI for the CLOTBUST ER study. “Based on strong interest level from the medical community, we are fortunate to have many of the world’s leading stroke centres participating in this pivotal phase III study to conclusively demonstrate the therapeutic benefit of this therapy and positively impact the future of emergency stroke treatment.”

“The medical community is eager to obtain access to new technologies to improve the outcomes of patients that are affected by the devastating effects of ischemic stroke,” said Carlos Molina, MD, professor and director of Neurology, Vall d’Hebron Hospital and chairman of the Steering Committee for the CLOTBUST ER study. “There have been very few treatment advances since tPA was originally approved in the US in 1996. If validated in this phase III clinical study, the Clotbust ER will serve as a major advancement in stroke care, providing clinicians with a new and novel treatment option to improve the clinical outcomes of stroke patients worldwide.”

Cerevast Therapeutics, Inc. is focused on the development of SonoLysis for the treatment of acute ischemic stroke and other vascular disorders.