NEW ORLEANS—A novel self-expanding stent currently under review for FDA approval outperforms the approved Merci clot retrieval device, according to results of the first randomized pivotal trial directly comparing cerebral revascularization devices.
A total of 60.7 percent of patients with acute ischemic stroke treated with the Solitaire device achieved successful revascularization without symptomatic intracranial hemorrhage (ICH), compared with 24.1 percent of patients treated with Merci, principal investigator Jeffrey L. Saver, MD, director of the University of California, Los Angeles Stroke Center, reported. [For more detailed findings, see “Data Comparing Solitaire and Merci Devices.”]
The Solitaire With the Intention for Thrombectomy (SWIFT) trial was halted early, after 113 of the planned 200 patients were enrolled, on recommendation of the data safety monitoring board due to “overwhelming” benefits in the Solitaire arm, Dr. Saver said here at the American Stroke Association's International Stroke Conference.
“For every five patients treated with Solitaire vs. Merci, one more patient avoids a fatal outcome. For every four patients treated with Solitaire rather than Merci, one more has a good neurological outcome,” he said.
SWIFT, an active-comparator, non-inferiority study, “is only the second positive randomized stroke trial in my 20-year trial experience; the first was with tPA,” Dr. Saver said.
Patients with acute ischemic stroke at 18 hospitals were randomized to either Solitaire or Merci within eight hours of the onset of stroke symptoms. On average, the time to treatment was 4.9 hours for Solitaire and 5.3 hours for Merci.
The two arms were well-matched except there were significantly more patients with atrial fibrillation in the Merci arm (67 percent vs. 45 percent).
The primary efficacy endpoint was successful recanalization with no symptomatic ICH, “and there was a highly significant advantage of Solitaire versus Merci,” Dr. Saver said.
The percentage of patients achieving good neurological outcomes at 90 days was also significantly higher in the Solitaire arm. Good neurological outcome was defined as a modified Rankin Scale (mRS) score of 2 or less, a mRS score no higher than the prestroke score if it was higher than 2, or an improvement in the NIH Stroke Scale score of 10 or more.
Additionally, the 90-day mortality rate was significantly lower in the Solitaire arm, and the patients required fewer rescue efforts.
Overall, the rate of device-related and procedure-related serious adverse events was similar in the two arms.
There were three device fractures with Solitaire, two of which occurred during the learning curve, Dr. Saver said. There were no device fractures with Merci.
For Solitaire versus Merci, 2.7 patients had to be treated to prevent one symptomatic intracranial hemorrhage, 4.8 to prevent one more non-fatal outcome, and 4.0 to obtain an additional good neurological outcome.
“With these results we have, for the first time, a highly effective cerebral recanalization procedure for ischemic stroke. tPA only reopens arteries partially 40 percent of the time and completely 5 percent of the time. This device reopens arteries completely 60 percent of the time. It's a dramatic change, and once this becomes available I think it will be a game changer,” Dr. Saver said.
Solitaire has already been submitted to the FDA, and a decision is expected later this year. “The general expectation is that the FDA will approve it, and I think it willdrive further use of mechanical thrombectomy devices,” he said.
Joseph P. Broderick, MD, professor and chairman of neurology at the University of Cincinnati, said the Solitaire device appears to be an incremental improvement over the Merci device, but noted that Penumbra, an aspiration device, was not included in the study.
“Solitaire represents a step forward for removing clots. But devices do have risk, can damage the artery wall, or when grasping the clot, the clot can fragment off and travel to another artery. If we knew which patients benefit, that would be an advance for these devices,” he said.
Claudette E. Brooks, MD, assistant professor of neurology at West Virginia University in Morgantown, said: “Using a device vs. a more studied therapy is hard. We have so much data on tPA, and we prefer tPA. And tPA is still underutilized. We use it [tPA] in about 20 percent of eligible ischemic stroke patients, but that is not good enough.”
Other factors limiting broader use of the devices include getting patients to properly equipped centers and training of interventional staff. Cost of a hospitalization — about $28,000 for devices vs. about $12,000 for tPA or $7,000 for best supportive care — is an issue, but would not be a real barrier if doctors were convinced of the utility of the devices, the experts said.
In response to a question, Dr. Broderick said that his team has not analyzed whether the percentage of patients having good neurological outcomes is different for patients treated before and after three hours, but that his impression is that there is “no real difference.”
The big question, Dr. Broderick and other experts said, is whether any of these devices improve outcomes for patients with acute ischemic stroke compared with tPA or even best supportive care alone.
Dr. Broderick is heading one of two trials addressing the questions. International Management of Stroke 3, or IMS3, is a randomized, open-label, multicenter phase 3 trial comparing IV tPA and intra-arterial (IA) tPA to IA tPA alone within three hours of stroke symptom onset. Doctors can use the Merci, Penumbra or Solitaire devices. The NINDS is sponsoring the trial.
Another NINDS-funded phase 3 trial known as MR RESCUE is comparing Merci to medical management.
Lee H. Schwamm, MD, vice chair of the department of neurology at Massachusetts General Hospital, said: “To have wide scale adoption of clot removal, we need a trial that shows it is more effective than medical therapy. If MR RESCUE is negative, then it may be a barrier to adoption [of any of these devices], especially in the era of cost containment.
“Many in the community believe that in the right hands and the right patients, these devices can be very effective. However, in the wrong hands or wrong patients, they can cause a lot of injury or death,” he said.
WHAT THE EXPERTS SAY ABOUT THE NEW DATA
BENEFITS: RETRIEVAL DEVICES
Why use a retrieval device for removing clots after stroke? Tissue plasminogen activator (tPA) is the preferred treatment for ischemic stroke, but it must be given within 4.5 hours of symptom onset, and its benefits begin to taper off after just three hours, Jeffrey L. Saver, MD, director of the University of California, Los Angeles Stroke Center, told Neurology Today. The window of opportunity is even shorter in elderly patients. When tPA cannot be used, neurologists may opt for mechanical removal of clots, which can typically be done for up to eight hours of symptom onset.
Currently there are two FDA approved devices for mechanically removing clots from blood vessels during or after a stroke: Stryker/Concentric Medical's Merci Retriever and Penumbra's Penumbra System.
In Europe, other devices are available, including Covidien's Solitaire and Stryker/Concentric Medical's Trevo. Dr. Saver has received research grants from, and served as a consultant to, Covidien, which funded the SWIFT trial.
Dr. Saver said Merci uses a tiny corkscrew, guided by a balloon-tipped catheter, to snare and remove clots.
In attempting to make it as safe as possible, the designers used a helical shape to reduce pressure on the arterial wall, he said. But the design had an unintended flaw: “If the clot sticks to the wall, the coil tends to straighten out and pull through the clot without engaging it,” Dr. Saver said.
In contrast, Solitaire “is a kind of columnar metal cage enmeshed with multiple points of contact, or struts. When expanded, it engages the clot at multiple strut points, which may be why it is more often effective in pulling the clot out,” he said.
Solitaire is inserted into the clot using a thin catheter, traps the clot in the stent, and then the stent and the clot are removed together, restoring blood flow. It is intended for vessels from 2 mm to 5.5 mm.
Trevo uses a retrievable and non-deployable stent-like device that is designed to act as retriever.
Penumbra uses suction to grab the blood clot and remove it from the body, an approach designed to minimize injury to the blood vessel wall. The device can be used up to eight hours after the onset of stroke.
FROM EUROPE: FINDINGS ON TREVO, A SECOND-GENERATION DEVICE FOR STENT RETRIEVAL
Also at the American Stroke Association International Stroke Conference, European researchers reported that Trevo Stentriever, a second-generation device that uses a stent retrieval system, performed well in a nonrandomized phase 2 trial, with partial or complete reopening of vessels achieved in 91.7 percent of 60 patients.
In the 60-patient, European, multicenter, prospective, single-arm TREVO (Thrombectomy Revascularization of large Vessel Occlusions) trial, the time from symptom onset to arterial puncture was 4.5 hours for 77 percent of patients, with the rest treated within 8.0 hours.
The primary endpoint was recanalization, and post-procedure, 91.7 percent of patients had at least thrombolysis in cerebral infarction [TICI] 2a blood flow (partial filling [<2/3] of the entire vascular territory) and 78 percent had at least TICI 2b flow (complete filling of all of the expected vascular territory, but filling slower than normal).
In addition, 55 percent achieved functional independence, defined as a modified Rankin score of 0 to 2 at 90 days. Serious adverse events occurred in 5 percent of patients, including one device-related perforation.
“This was not a randomized study, but it was very encouraging for further development,” said principal investigator Nils Wahlgren, MD, head of the clinical stroke program and stroke research unit at Karolinska University Hospital in Stockholm. The phase 3 TREVO-2 trial is ongoing.