Medical Device Daily Associate

Preliminary results from a trial presented at the International Stroke Conference of the American Stroke Association (Dallas) being held in Kissimmee, Florida, could have a significant impact on how ischemic stroke patients are treated in the future.

The results of the National Institutes of Health (NIH; Bethesda, Maryland)-sponsored Interventional Management of Stroke II (IMS II) trial were presented yesterday by principal investigators Joseph Broderick, MD, and Thomas Tomsick, MD, both of the University of Cincinnati, supporting a promising new treatment for victims of ischemic stroke that combines intra-arterial (IA) drug delivery with the more traditional intravenous (IV) approach. The study found that the combination treatment yielded much better outcomes than treatment with IV alone and forms the basis for a much broader Phase III study that is being planned.

The Ekos (Bothell, Washington) Micro-Infusion Catheter MicroLysus infusion system was used in 41% of the patients in the 73-patient trial to deliver the thrombolytic drugs directly to the clot. This device is unique because it incorporates ultrasound technology into the tip of a microcatheter to accelerate the dissolving of the blood clot.

The trial, co-sponsored by Ekos, investigated patients between the ages of 18 and 80 at 13 centers who presented with severe ischemic stroke. Each patient 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 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, patients 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 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% of the 34 patients receiving the ultrasound treatment. This was an improvement when compared with the IMS-I study, in which 55% 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 and not the Ekos device.

“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% relatively greater compared to IV-only tPA-treated subjects in IMS-I,“ said Broderick.

According to Ekos Chairman and CEO Peter Rule, while this is the second NIH-funded study combining IV/IA therapy for the treatment of ischemic stroke, it is the first one his company has participated in, and he believes the use of the Ekos system has contributed to the improvement in outcomes between IMS I and IMS II, and has laid the groundwork for a Phase III study.

He told Medical Device Daily that while the results of the first IMS study were positive, the data “wasn't as good as [the NIH] wanted.“

Instead of going straight into a Phase III randomized trial, Ekos suggested that Broderick and Tomsick – who were the principal investigators of IMS-I – do a second study using the company's ultrasound system to see if it worked better than a “plain vanilla catheter“ for the delivery of tPA to the brain.

Ekos' products include both the Micro-Infusion Catheter and the Lysus Peripheral Infusion System, which are cleared for use in dissolving blood clots in the periphery to treat patients with peripheral arterial occlusions and deep vein thrombosis.

The company bases all its products on the same ultrasound technology platform. That ultrasound technology is then adapted to the appropriate catheter delivery technology for either the leg or the brain.

For the neurovascular application, the Ekos microcatheter is able to better target a clot than the standard IA drug delivery. The ultrasound, via acoustic pressure, helps push the tPA into the clot. “It's able to get a higher surface area,“ said Rule. “In other words, it's not just dissolving the outside of the clot [as with a standard IA drug delivery system], it's dissolving the outside and the inside of the clot.“ As a result of this ultrasound action, “the same drug has a higher surface area and therefore, acts faster,“ which can be critical in the time-sensitive treatment of an ischemic stroke.

According to Rule, Tomsick has said that the flow rate or recanilization for IMS II “is the most successful trial in the history of ischemic stroke therapy,“ with a recanilization rate of 77% for the Ekos-treated patients. “No technology or trial has ever reported anything in the 70s,“ he said, adding that doctors only chose to use the Ekos system “for the toughest cases in the trial.“

He also noted that the clinical outcomes and safety data were better for the IMS II study when compared with IMS I.

Based on the success of IMS II, in September 2005, the National Institute of Neurological Disorders – a unit of the NIH – gave the University of Cincinnati a $17.4 million grant to coordinate the IMS III trial, which will study up to 900 U.S. and Canadian stroke patients – with interim analysis after every 225 patients are enrolled – at up to 40 centers.

Study participants in that trial 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 device called the Merci Retriever, an FDA–approved device made by Concentric Medical (Mountain View, California) that is designed to remove blood clots.

Rule said he expects the IMS III trial will begin in April but he doesn't think it will need to enroll the full 900 patients because, based on the data that he has seen thus far for the IMS I and IMS II trial, the trial probably will be stopped early.

“We would tell you that, based on the data that we know, it's going to finish well sooner than the 900 [patients].“

Rule said that if the company's device is approved for use in ischemic stroke treatment, the system could ultimately be used for an annual patient population representing nearly 500,000 in the U.S alone.

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