The findings, says the University of Cincinnati's Joseph Broderick, MD, co-principal investigator of the study, are encouraging and support a much broader phase-3 trial planned to begin soon.
Dr. Broderick, chair of the neurology department at the University of Cincinnati (UC) and co-principal investigator Thomas Tomsick, MD, director of neuroradiology at UC and Cincinnati's University Hospital, presented their findings today at the International Stroke Conference in Kissimmee, Fla. The study was co-sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) and EKOS Corporation.
The study, known as Interventional Management of Stoke Study or IMS-II, involved 73 participants between the ages of 18 and 80 treated in 13 participating centers and suffering from severe ischemic stroke. Each was given lower than standard doses of tissue plasminogen activator (tPA) during a 30-minute period within three hours of the onset of stroke.
Subjects were then immediately taken for an angiography where a microcatheter (small tube) was placed into a groin artery and threaded to the site of the blocked artery in their brain. Twenty-one participants without a visible and treatable clot received no additional therapy. The remainder of participants (52) who had visible, treatable clots was treated with up to 22 milligrams of additional tPA delivered through the catheter directly to the blockage.
Whenever possible, they were also given a low-energy ultrasound treatment at the site of the clot. The ultrasound, which attempted to break up the clot, was administered using the EKOS Micro-Infusion Catheter MicroLysus infusion system. In 18 participants, where the EKOS MicroLysus catheter could not access the clot, a standard catheter was used to deliver tPA to the clot site.
Partial or complete reopening of the blocked brain artery occurred in 69 percent of the 34 patients receiving the ultrasound treatment. This was an improvement when compared with the IMS-I study, in which 55 percent of patients involved achieved partial or complete reopening of the blocked artery. The IMS-I study used only a microcatheter to deliver tPA directly to the location of the stroke-causing clot.
"After adjustment for differences in baseline stroke severity, age and time-to-treatment, the likelihood of IMS-II subjects attaining functional independence at three months was 65 percent relatively greater compared to IV-only tPA-treated subjects in IMS-I," Dr. Broderick says.
The mortality of the IMS-II participants (16 percent) was identical to those in IMS-I. Participants in the earlier NINDS tPA Stroke Trial, which tested the benefit of tPA administered within three hours after onset of stroke, had a 21 percent mortality. Dr. Broderick noted, however, that the rate of bleeding in the brain that resulted in worsening of the participants' condition during the IMS-II study was 11 percent as compared to 6.3 percent in the IMS-I study.
"A combined analysis of IMS I and II studies to investigate the effect of treatment on patient outcome, reopening of arteries, and safety is being planned," says Dr. Broderick.
Strokes affect about 600,000 Americans each year and are the third leading cause of death in the United States after heart disease and cancer. There are two main types of stroke: ischemic, which results from blockage of a blood vessel, and hemorrhagic, which is caused by bleeding.
Quickly reopening clogged brain arteries in stroke patients is important because the longer the blood supply to the brain is blocked, the more likely long-lasting brain damage will occur.
"Stroke studies such as the IMS are advancing our knowledge about stroke so that ultimately more lives may be spared," Dr. Broderick says. "More importantly, quality of life is preserved by preventing the debilitation that comes with permanent brain damage."
In September 2005, NINDS awarded the University of Cincinnati a $17.4 million grant to coordinate the next phase of the study--the IMS-III trial--which will study about 900 U.S. and Canadian stroke patients. 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 (and used with or without ultrasound to break up clots), or a reduced tPA dose and removal of the clot using a mechanical device called a Merci Retriever, a Food and Drug Administration-approved device designed to remove blood clots.
In addition to funding from the NINDS and EKOS Corporation, the study received study medication from Genentech, Inc. Neither Dr. Broderick nor Dr. Tomsick holds any financial interest in EKOS or Genentech.
Drs. Broderick and Tomsick are members of the Neuroscience Institute in Cincinnati, a collaborative effort of nine academic departments at the UC College of Medicine, University Hospital and independent physician practice groups.