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FDA panel: More data needed for embolic protection device for TAVR procedures
The FDA’s Circulatory System Devices Panel said despite flaws in current data, de novo classification may be warranted for an embolic protection device for prevention of stroke during transcatheter aortic valve replacement procedures.
Panel members stated that current efficacy data, based on findings from MRI scans, are not strong enough to assess how well the device might protect against stroke. However, many said the device serves an important need and may be worth allowing on the market because it is safe and appears to prevent disastrous outcomes.
The problem with the data “is more about the imperfection of the device than a flaw in the concept,” panelist David D. Yuh, MD, from Stamford Hospital, Stamford, Connecticut, said during the meeting.
No votes were taken by the panel as part of Claret Medical’s request for de novo classification of the device (Sentinel); rather, the FDA asked the panel for insights to help the agency make its decision.
A de novo classification is a designation the FDA may grant enabling clearance for a novel medical device of low or moderate risk for which there is not a substantially equivalent product on the market. Devices granted de novo classification are not eligible for 510(k) clearance, which requires substantial equivalence to an existing product, but their applications are not subject to the same level of scrutiny as higher-risk devices without substantial equivalence to an existing product, which must go through the premarket approval process.
Claret Medical asked the FDA for de novo classification of the device based on the results of the SENTINEL trial, which found that use of the Sentinel embolic protection device in patients undergoing TAVR was safe, but was not statistically significant for efficacy, defined as reduction in median new lesion volume in protected brain territories on MRI scans between 2 and 7 days vs. use of no embolic protection device.
During the hearing, the FDA asked panel members whether the device was safe, whether diffusion-weighted MRI results from the SENTINEL trial were an acceptable surrogate for clinical stroke, how future trials of the device should be designed, how to report the effectiveness outcomes of the device in the labeling, what the clinical significance of debris capture might be, how to interpret the neurocognitive outcomes from the SENTINEL trial, whether the proposed indications and labeling were appropriate, whether benefit–risk considerations were adequate and what data should be collected postmarket if de novo classification is granted.
“I’m not concerned about a signal that relates to potential harm” from use of the device, said panel member Joaquin E. Cigarroa, MD, from Oregon Health & Science University, Portland.
Future trials should “not just have imaging outcomes, but have neurological outcomes in a systematic way,” John C. Somberg, MD, from Rush University Medical Center, Lake Bluff, Illinois, one of several panelists who expressed dissatisfaction with diffusion-weighted MRI endpoints as a surrogate for stroke, said during deliberations.
Panelist Jeffrey S. Borer, MD, from State University of New York Downstate Medical Center, said although “strokes trended in the right direction, though there were too few of them to draw conclusions [from the SENTINEL trial], and I would be happy with less cognitive dysfunction, the correlation [with the imaging endpoint] was quite weak. We should rethink things in terms of the imaging if we stay with that direction.”
Therefore, Borer said, the imaging results cannot be considered clinically meaningful.
Although the currently available outcomes may not be clinically significant, “I don’t think they’re due to random variation, either,” said panel member Guerry M. Peavy, PhD, from the University of California, San Diego. “There are things we can learn from the results that have occurred.”
A long-term registry measuring stroke and neurocognitive function of people who received the device and those who were considered for the device but did not receive it might be a good idea, Somberg said. – by Erik Swain
Disclosure: The members of the FDA’s Circulatory System Devices Panel report no relevant financial disclosures.
Perspective
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It’s not a surprise that this device was said to be safe. It has been shown that we did not start causing strokes while we were trying to prevent them. It was disappointing that the device did not affect clinical stroke, but not hugely surprising. Clinical stroke during the procedure is such an uncommon occurrence now. The debate about the MRI-derived data has been ongoing. We know the diffusion-weighted images we are seeing represent small areas of cell necrosis in the brain. Most of us think that can’t be good, but we don’t know exactly how bad it is. The same images are seen in surgical aortic valve replacement, albeit slightly less often than in TAVR, and we know there is no real difference in clinical stroke between TAVR and surgery; in fact, TAVR has been on the lower side of surgery in the most recent randomized trials.
The panel’s conclusion that this device is safe is correct. The panel’s conclusion that the device may prevent catastrophic stroke in uncommon cases is correct. The counter to that is, if we use this device in all TAVR procedures, we are going to add a lot of cost to a procedure that is already hard to break even on for many institutions. Then the question is, will operators be allowed to use the device at their discretion, or, as with carotid stenting, will they not be paid for the procedure unless they use it? To me, that would be a step too far, as there is no real evidence to support it. Approval of the device is reasonable, but then it will fall to clinicians to determine if they should add it to every commercial case performed. If that is done, the institution might lose money on the procedures. Another consideration, however, is what happens if the device is not used, and the patient has a stroke and sues, claiming it could have been prevented?
As a practitioner in this field, I am very concerned about neurologic injury, particularly as TAVR moves to lower-risk patients. If a 70-year-old patient after TAVR has diffusion-weighted lesions that go away after 3 months, do they later get dementia earlier than they would have otherwise? It’s hard to tell, and it’s something we all worry about.
If the device gets approved, I would like to see its use captured in the Society of Thoracic Surgeons/American Cardiology Transcatheter Valve Therapy registry data. I would also require that if it is going to be used, an NIH Stroke Scale score be calculated before and after the procedure, and if it changes, a neurologist should see the patient. Long-term registry follow-up is needed because strokes are uncommon events and the only way to capture uncommon events is through large registries. I would require that participation in TVT be required if reimbursement is to be given for the device, and that neurologic screening be performed.