An international, Phase III clinical trial studying ultrasound in combination with a clot-busting medication to treat acute ischemic stroke has begun at The University of Texas Health Science Center at Houston (UTHealth).
The randomized, double-blinded, placebo-controlled trial will recruit 830 patients in approximately 60 sites around the world. The UTHealth Medical School site was the first in the world to enroll a patient, Enrique Chapa, 75, of Houston.
The only current therapy for stroke caused by a blood clot in an artery is intravenous tissue plasminogen activator (tPA). The ability of transcranial Doppler ultrasound energy to facilitate the break down of blood clots was noted first at UTHealth and results of a Phase 2 safety and efficacy study were published in the New England Journal of Medicine in 2004.
"We hope this will be the definitive trial to see if the delivery of ultrasound in combination with tPA results in better outcomes than the use of tPA alone," said Andrew Barreto, M.D., assistant professor of neurology at the UTHealth Medical School and the North American principal investigator for the trial. "We will be assessing if the treatment leads to less disability and more independence for stroke victims."
The trial is called Combined Lysis of Thrombus with Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization in Acute Ischemic Stroke (CLOTBUST-ER). It uses UTHealth technology licensed to Cerevast Therapeutics, Inc., which developed an operator-independent head frame that delivers ultrasound through 16 individual probes. The device, called ClotBust-ERTM, recently underwent an NIH-sponsored Phase II safety study. A sham device is used for the placebo-controlled portion of the trial.
Because the trial is blinded, no one knows if Chapa received the actual ultrasound or the sham device, but his family didn't hesitate to enroll him after he collapsed at home Monday, May 20.
"He was watching the Astros and when he went to stand up, he just fell in slow motion," said his wife Tommie Chapa. "He thought his ankle gave out on him but my son Richard noticed that he couldn't move his right leg and thought he was having a stroke so we called 911."
The study's research assistant, Hari Indupuru, explained the study to them while Chapa was in the emergency room at Memorial Hermann-Texas Medical Center.
"Hari told us what they would do. He explained that it would massage the area and help the medicine work faster," Chapa's son Michael Chapa said. "We thought that even if he didn't get the ultrasound, if it's something to help in the future, great, I'm all for it. You'll do anything that will help your father get back healthy."
By the following Saturday, Enrique Chapa began to feed himself, communicate with family members and work the television control. He is currently receiving rehabilitation.
Barreto said the head frame device makes the application of the ultrasound easier. "The first safety study was done with a diagnostic handheld probe placed against the temple and medical personnel had to be trained to properly administer the ultrasound," Barreto said. "Now with Cerevast's device, the operator-independent head frame can be placed on the head with minimal training by any emergency room staff member."
The Phase II study published in the November, 2004 issue of the New England Journal of Medicine was led by Andrei V. Alexandrov, M.D., while he was at UTHealth. Results showed a 38 percent rate of arterial recanalization using ultrasound and tPA, compared 13 percent recanalization with tPA alone.
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