The study, to be led by Joseph Broderick, MD, chair of UC's neurology department, and Thomas Tomsick, MD, director of neuroradiology, will be the first randomized trial of its type in acute ischemic stroke. It will also be the first to compare new procedures against the standard approach to clear clogged brain arteries, the cause of ischemic stroke.
Opening clogged arteries in stroke patients quickly is important, because the longer the blood supply to the brain is blocked, the more likely long-lasting brain damage will occur.
Known as the Interventional Management of Stroke (IMS) III Trial, the study will compare results in about 900 U.S. and Canadian stroke patients treated either with the widely used intravenous, clot-busting drug tissue plasminogen activator (tPA), or with a combination of approaches.
Study participants will be randomized to receive either standard doses of tPA, a reduced tPA dose delivered to the clogged brain artery through a catheter (tube) that uses ultrasound to break up clots, or a reduced tPA dose and removal of the clot using a mechanical device called a Merci Retriever.
"Cardiologists have used combinations of drugs and devices to unblock heart arteries for several years. We hope that this trial can be the first step in that direction for acute stroke," Dr. Broderick said.
"We're hoping this will lead to a paradigm shift in stroke treatment, from the standard tPA dose given intravenously to less tPA and a more interventional approach, which will be whatever is needed to open the artery," Dr. Broderick added. "This will mean that instead of just using an IV, centers that have the expertise will be able to do a more complete job. I think this will be the next major step in stroke treatment, but we must test it thoroughly to ensure it's appropriate.
"We're essentially building a toolbox," Dr. Broderick said. "One or both of these more interventional procedures may be useful and will be added to the treatment options. But they probably won't be the last.
The field is changing so rapidly, if new approaches arrive during the next five years, they could be included in the study."
Pilot studies at U.S. and Canadian centers found that the combined approach was encouraging enough compared with the standard tPA treatment to merit this new Phase III, which will be conducted at 50 centers in the United States and Canada, including 11 hospitals in the Greater Cincinnati/Northern Kentucky area.
In the late 1980s and mid-1990s, UC investigators played a leading role in developing and testing tPA as a treatment for ischemic stroke. They determined that if a stroke patient can be evaluated and treated with intravenous tPA within three hours, there was a good chance of full recovery.
However, although this represented a major step forward, intravenous tPA still does not open blocked brain arteries in many patients with larger strokes. So, since 1994, UC has initiated and coordinated three acute stroke trials that compared intravenous tPA administration with tPA delivery through a catheter.
The advantage of giving tPA intravenously, Dr. Broderick explained, is that it can be started quickly by any knowledgeable physician in any hospital with a CT (computerized tomography) scanner. Targeted injection of the clot-busting drug through a catheter, however, provides better opening of blocked arteries than intravenous tPA alone.
The new trial, funded by the NIH's National Institute of Neurological Disorders and Stroke, will involve physician and nurse investigators from four UC departments--neurology, emergency medicine, neurosurgery and radiology--with Drs. Broderick and Tomsick as principal investigators. Data management and statistical analysis will be coordinated at the Medical University of South Carolina.
There are two main types of stroke, the third leading cause of death in the United States after diseases of the heart and all forms of cancer, which affect about 600,000 Americans each year. Ischemic stroke, the subject of the IMS III study, results from blockage of a blood vessel. Hemorrhagic stroke is caused by bleeding.