Safety, not benefit, carries the day
by
Reporter, MedPage Today/CRTonline.org
Despite the cloud of questions surrounding its clinical efficacy, an FDA advisory panel overwhelmingly recommended approval for the Sentinel Cerebral Protection System. As a de novo application for a lower-risk device, the Sentinel did not require a formal panel vote.
Discussants cited the lack of alternative options and the low safety risk as reasons to give the simple filter the green light.
“The risks are as low as they can be for any device we introduce to an arterial circulation,” said Joaquin E. Cigarroa, MD, of Oregon Science and Health University in Portland.
“It does what it says it was going to do; it gets junk so it won’t get to the brain. It’s basically like my taking aspirin every day. If I were to have this kind of valve procedure I would want this — it won’t hurt,” commented patient representative Phillip Posner, PhD.,”the only thing is the cost.”
The device does not, however, reduce the risk for stroke. Rates of major adverse events were not lower if patients got TAVR with the Sentinel filter in place, according to the randomized SENTINEL trial that served as the focus of today’s discussion.
Furthermore, new lesions appearing within a week after the procedure were of a similar size between groups (median in protected territories 102.8 mm3 versus 178 mm3for control, a 42.2% reduction, though not statistically significant). When all territories were analyzed on an intention-to-treat basis, what was not statistically significant grew even less so (294 mm3 versus 309.8 mm3, a 5.1% reduction); per-protocol data actually showed larger new lesions among protected patients.
Consisting of a proximal and a distal filter to capture embolic material during transcatheter aortic valve replacement (TAVR), the Sentinel from Claret Medical shields cerebral territories supplied by the carotid arteries bilaterally and the right vertebral artery — all the while leaving the left vertebral artery unprotected.
The only win for the device was that it managed to cut new lesion volume by more than 30% within protected territories, compared with control. No difference between test and control arms were observed with regards to Neurocognitive Battery Composite Z-scores.
The SENTINEL trial randomized TAVR patients to embolic protection without diffusion-weighted MRI (n=124), embolic protection with diffusion-weighted MRI (n=121), and no protection (n=119).
Calling the data “grossly underpowered” and “very skewed,” the discussants noted the high rate of missing imaging data (25% of test arm, 18% of control arm) that exacerbated a trial underpowered to detect differences in stroke rates and one that necessitated the use of diffusion-weighted MRI as a surrogate endpoint.
And the device was not proven to be completely safe: while the manufacturer claimed that 99% of devices captured some degree of debris in SENTINEL, panelists couldn’t be sure that it captures all debris — or that it didn’t dislodge some debris itself.
The discussants recommended extended follow-up on patients who received the Sentinel if the FDA were to approve the device.
“As TAVR moves to younger patients, the worrying issue is not just stroke — but debris and its impact longitudinally,” noted George W. Vetrovec, MD, of Richmond’s Medical College of Virginia.
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View original article on MEDPage Today – http://www.medpagetoday.com/neurology/strokes/63389