Novel Aspirating Device Reportedly Improves Reperfusion in Stroke Patients
ARTICLE IN BRIEF
A novel aspirating device reduced clot burden, resulting in an 82 percent recanalization rate within eight hours in patients with acute ischemic stroke.
NEW ORLEANS—A novel device that suctions out blood clots provides safe and effective revascularization within eight hours of acute ischemic stroke, a prospective, phase 2, single-arm study indicates.
Called the Penumbra System, the aspiration device “was effective in reducing clot burden, resulting in an 82 percent recanalization rate,” Cameron G. McDougall, MD, chief of endovascular neurosurgery at the Barrow Neurological Institute in Phoenix, reported here in February at the American Stroke Association's International Stroke Conference.
While the trial was not powered to show statistical significance for clinical outcomes, “trends toward better outcomes when vessels were opened were consistently observed across all neurological and functional measures,” he said.
The results of the Penumbra, Inc.-sponsored trial led to FDA approval of the aspiration catheter in December 2007. However, neurologists at the meeting, who were not involved with the study, pointed out that approval of the device did not require proof of clinical benefit.
Philip B. Gorelick, MD, John S. Garvin Professor and head of the department of neurology and rehabilitation and director of the Center for Stroke Research at the University of Illinois College of Medicine in Chicago, said: “Approval of a device is different from drugs, where you need to show the new agent improves on or at least is comparable to other treatments. With devices, you just have to show that they do what they are supposed to do and that they are safe.”
In the current trial, Dr. Gorelick said, the primary endpoint was revascularization, not clinical outcome, “the idea being that reperfusion is what it takes to get improvement.”
Dr. McDougall said the device was designed with three components: a reperfusion catheter designed for optimal navigation and aspiration, a separator designed to clean out the catheter and keep its tip clear, and a thrombus-removal ring designed to capture any calcified clots that remained after aspiration.
“As designed, the device included an aspiration catheter, as well as a second grabbing device,” he said. But “we never really needed the extraction device and it resulted in improved outcomes in only one patient.”
The 24-center international study, which was designed during meetings with FDA officials, involved 125 patients with a baseline score of eight points or higher on the 42-point NIH Stroke Scale (NIHSS), where higher scores indicate worse severity. Also, patients had to have either no perfusion or faint antegrade coronary flow beyond the occlusion, as indicated by scores of 0 and 1 on the TIMI (Thrombolysis in Myocardial Infarction) scale.
Occlusion of a treatable intracranial vessel and treatment had to be initiated within eight hours of stroke symptom onset, which Dr. McDougall noted is beyond the three-hour treatment window for tissue plasminogen activator (tPA). Patients seen within three hours of symptom onset who were refractory to tPA therapy were also eligible for the trial.
The mean age of the participants at baseline was 64.5 years, the mean NIHSS score was 17.6 points, and the mean score on the six-point modified Rankin Scale was 4.5 points, indicating moderately severe to severe disability.
The primary endpoints of the trial were partial or complete revascularization of the primary occlusion site and the incidence of procedure-related serious events.
Use of the Penumbra System resulted in successful revascularization in nearly 82 percent of the treated vessels. Also, 41.6 percent of the patients had a favorable outcome, defined as improvement of four points or more on the NIHSS at discharge or a 30-day modified Rankin Scale score of two points or less.
One in four patients had a modified Rankin Scale score of two points or less at 90 days, Dr. McDougall said.
There were adverse events in four patients, but none of those events were attributed to device failure or breakage, he said. At 24 hours, 35 patients (28 percent) had intracranial hemorrhage. Fourteen (11.2 percent) were symptomatic, defined as having CT evidence of a bleed and a deterioration of four points or more on the NIHSS, he said.
At 30 days, 26 percent of patients had died from any cause; at 90 days, all-cause mortality was 33 percent. Dr. Gorelick said that these mortality rates are not unexpected given the severity of the patients' strokes at baseline as measured by the NIHSS.
As prospectively agreed upon with the FDA prior to the trial, outcomes from the 2005 trial of Concentric's MERCI (Mechanical Embolus Removal in Cerebral Ischemia), the only other mechanical device approved for clot removal, were used as historical controls.
That comparison showed that the Penumbra System was associated with a significantly better revascularization rate: 82 percent versus 48 percent for MERCI, Dr. McDougall reported. The incidence of device-related and procedural serious adverse events did not differ significantly between the two devices: 3 percent for the Penumbra System versus 7 percent for MERCI.
Dr. McDougall noted that newer generation MERCI devices are associated with recanalization rates of 60- to 70-percent. “As a first iteration, [Penumbra] compares favorably,” he said.
Larry B. Goldstein, MD, professor of medicine in the Division of Neurology and director of the Center for Cerebrovascular Disease and the Duke Stroke Center at Duke University in Durham, NC, said that the Penumbra System might be an option for “patients who don't qualify for tPA for one reason or another and have a clot that is potentially reachable.”
But, he added, the results of a single-arm study fail to help neurologists reach clinical decisions. “It's unclear how to translate the information into clinical outcomes,” said Dr. Goldstein. He and Dr. Gorelick agreed that a randomized controlled trial pitting the aspiration catheter against tPA or the MERCI device is needed.
In the meantime, Dr. Gorelick said: “It is exceedingly important that those employing the device talk to the patient, if that's possible, or the family, so they understand there are safety issues and that we still don't know whether outcomes such as stroke severity are improved.”