MADISON - The use of a synthetic drug derived from the saliva of vampire bats appears to extend the time window for treatment of acute ischemic strokes from the current three to nine hours after symptoms first appear, according to the results of a new international study.
The results of the DIAS trial (Desmoteplase in Acute ischemic Stroke), to be presented Feb. 5 at the International Stroke Conference in San Diego, show that the drug desmoteplase is effective in preventing brain damage from stroke if administered between three and nine hours after symptoms begin. The University of Wisconsin Medical School is one of the test sites for the ongoing twin U.S. study, DEDAS (Dose Escalation study of Desmoteplase in Acute ischemic Stroke), designed to identify the appropriate dosage and effectiveness of the drug.
Howard Rowley, associate professor of radiology at the UW Medical School, is the lead radiologist for the DEDAS study nationally and a member of the UW team researching it on patients in Madison. Magnetic resonance imaging (MRI) findings of the study will be presented by Steven Warach, director of stroke at the National Institutes of Health. George Newman, professor of neurology, and Ross Levine, associate professor of neurology, are the primary UW investigators on the study.
"This new approach to acute stroke treatment is novel in two ways: It uses an improved clot-dissolving drug, and also takes advantage of new MRI techniques to help select the right patients for treatment," says Rowley. "The results of the DIAS study are even more exciting as they show specifically how the use of the drug significantly extends the time during which treatment can begin after the onset of stroke symptoms, from three hours to nine hours."
Desmoteplase is a genetically engineered version of a blood clot-dissolving protein from the saliva of the vampire bat, Desmodus rotundus. Desmoteplase is able to dissolve a blood clot without affecting the rest of the body's clotting system and without increasing the risk of intracranial bleeding.
The DIAS study was a multi-center, Phase II study. Forty-four hospitals from Europe, Australia and Asia participated and 25 centers recruited a total of 102 patients. Patients eligible for standard treatment received it, but those who met study criteria and were between three to nine hours of initial symptoms were randomly assigned to receive either desmoteplase or a placebo. Neither the researchers nor the patients knew which substance the patient received. The sister study, DEDAS, is ongoing in 17 centers and expects to recruit more than 100 patients in the United States, with the same study design. In both studies, MRI was used to identify patients who have the potential to benefit most from this therapy.
By imaging the brain of stroke victims, the doctors were able to better determine if the patient might be a candidate for desmoteplase. For eligible patients, administering desmoteplase allowed the blood flow in the damaged area of patients' brains to be re-established and the area of damage limited. Ultimately, an effective but safe dosage of desmoteplase was identified, resulting in an extended time window (after the onset of stroke symptoms) of nine hours versus three.
"The impact of these results cannot be overstated," says Rowley. "Buying more time to treat stroke symptoms-and the ability to safely restore blood flow to the brain-means we can give acute stroke victims hope for a better outcome, even if having a stroke cannot be prevented. It also appears that new MRI techniques are key in helping to select the right patients for therapy."
Stroke is the third leading cause of death in Europe and the United States-behind heart disease and cancer. The treatment of acute stroke and its serious long-term disabilities is, up to now, only possible with an approved agent (t-PA, tissue plasminogen activator) that must be administered within three hours after the onset of stroke symptoms, allowing only a small fraction of all stroke patients to benefit from such a therapy. With the findings of the DIAS study, more patients may benefit and reduce stroke's burden of disability, and help more people sustain a near normal life following a stroke-especially those individuals located in rural areas.
"This is the biggest breakthrough I've seen in 20 years," says Rowley. "It gives us the ability to treat a large number of patients for whom we currently have no therapy, and it also gives us the future possibility of combining therapies by initially opening the vessel with desmoteplase and then piggy-backing a second therapy to reduce the damage to neurons themselves."
Phase III of the study is expected to begin in upcoming months with the goal of proving clinical effectiveness to get one step closer to FDA clearance.
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