NCHR’s Testimony to FDA on the TriGUARD 3 Device

August 3, 2021

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Meg Seymour, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

Today, you are asked to determine whether the TriGUARD 3 device is substantially equivalent to its predicate device, Sentinel. Keep in mind that there are several different standards for substantial equivalence, and one of them is the benefit to risk ratio. For patients and their physicians, that’s the most important one. And, unfortunately, that is even more complicated because the post-market research done on Sentinel indicates that it does not reduce stroke or transient ischemic attack, which was the intention. As FDA scientists note in the Executive Summary, the primary and supplementary data provided by the sponsor make it difficult to draw clear conclusions about substantial equivalence.

I would like to draw your attention to the limitations of the data regarding the effectiveness and safety of TriGUARD 3, based on its own data and in comparison to the predicate device.

Let’s start by talking about the effectiveness of the device. As FDA scientists note, the REFLECT trial of TriGUARD 3, and the SENTINEL trial used different primary effectiveness endpoints, making it difficult to draw a comparison between the two. Most important, the primary effectiveness endpoint for TriGUARD 3 was not met in the REFLECT Phase II trial. TriGUARD 3 did not meet its primary effectiveness endpoint of all-cause mortality and/or stroke at 30 days.

Now I’ll focus on safety. Both the Sentinel and TriGUARD 3 devices met their primary safety endpoint. However, a closer look at the data shows that TriGUARD 3 did not show the benefits compared to the control group that were shown for the Sentinel device. In fact, the trends were in the opposite direction, with the control group having better outcomes than TriGUARD. For example, at 30 days, 11.2% of patients in the TriGUARD 3 group had a stroke, which is more than twice the rate of stroke for the control group, which was 5.3%. Similarly, the 30-day death rate was almost twice as high for those randomized to receive the TriGUARD 3 – 3.4% — compared with 1.8% of the control group of standard care. The SENTINEL trial showed a nonsignificant trend favoring the predicate device over control, but the REFLECT trial Phase II for the TriGUARD 3 device in question today, did not show such a benefit. So, the bottom line is the TriGUARD 3 device does not demonstrate safety compared to a control group receiving regular non-EPD care, without the potential benefit reported for the predicate device.

And, As noted in the American College of Cardiology’s online summary of the REFLECT II trial, bleeding and major vascular complications occurred at 5.7% and 7.0% in the TriGUARD 3 group, with none occurring in the control group. TriGUARD 3 showed no advantage over non-EPD protected TAVR procedure.

To further add to the poor quality of the data available, there were also modifications made to the device during the study. The sponsor has only presented real-world clinical evidence about the newly modified device, but you’re being asked to consider data from the REFLECT trial, which does not include patients with this modified version of the device. The only data available on the newly modified version is based on 50 patients treated at a single center, rather than data from a controlled, clinical trial. You are asked to determine whether the TriGUARD 3 device is substantially equivalent to the Sentinel device, but how can you determine that when the data from the REFLECT trial do not provide information on the most recent version of the device?

There is a lot of controversy about FDA standards for medical devices that have the potential to save lives, or cause death. Patients deserve better. FDA should not clear a potentially life-threatening device that did not meet its primary effectiveness endpoint and is not safer than the usual standard of care – and very possibly less safe. When asked to compare these data to those regarding the predicate device, the data do not show any of the benefits that had been reported for the predicate device. No matter how you look at it, the TriGUARD 3 device is not shown to be substantially equivalent or safe or effective and should not be cleared for market. Please consider this information during your discussion today.