TCT 2016: Cerebral protection device used during TAVR does not meet primary endpoint

A randomized trial found that an investigational cerebral protection device captured embolic debris in 99 percent of patients undergoing transcatheter aortic valve replacement (TAVR) and did not change their neurocognitive function.

However, the study did not meet its primary efficacy endpoint, which was the reduction in median new lesion volume in protected territories as assessed by MRI two to seven days after patients underwent TAVR. Patients who received the device also did not have significant improvements in neurocognitive functioning.

Study co-author Susheel Kodali, MD, presented the findings Nov. 1 in a late-breaking clinical trials session at the Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, D.C.

The results were simultaneously published online in the Journal of the American College of Cardiology. Claret Medical, which manufactures the Sentinel cerebral protection system used in the study, funded the trial.

The Sentinel cerebral protection system is not yet FDA-approved, but Claret Medical submitted a marketing application to the FDA in September for its approval. The device is designed to protect the brain during TAVR procedures.

“Despite not meeting its primary efficacy endpoint, the study does provide evidence of device safety and confirms the high-frequency of embolic debris capture with the Sentinel dual filter neuroprotection therapy,” Kodali said in a news release. “In addition, there are important lessons from this trial which should impact future research on neuroprotection during TAVR.”

In this study, known as SENTINEL, the researchers enrolled 363 patients at 17 centers in the U.S. and two centers in Germany. The patients had severe symptomatic aortic stenosis and were undergoing TAVR. They were randomized in a 1:1:1 ratio to a safety group in which they only received the Sentinel, a test group in which they received the Sentinel and underwent imaging and the control group in which they only received imaging.

The test and control groups had a brain MRI using a 3 Tesla scanner at baseline, two to seven days post-TAVR and 30 days post-TAVR. All of the patients also underwent rigorous neurocognitive evaluations after undergoing TAVR and then at 30 and 90 days post-TAVR. The neurocognitive assessments evaluated bi-hemispheral and hemisphere-specific attention, executive function, processing speed, working memory, visual memory, mental status and depression.

The median age was 83.4 years old, and 52.1 percent of patients were females. In addition, the median Society of Thoracic Surgeons score was 6 percent, while 31.7 percent of patients had atrial fibrillation and 5.8 percent had a prior stroke.

During the study, the researchers used four TAVR devices: the Sapien XT (Edwards Lifesciences) in 17.8 percent of patients, the Sapien 3 (Edwards Lifesciences) in 52.4 percent of patients, the CoreValve (Medtronic) in 3.9 percent of patients and the Evolut R (Medtronic) in 25.9 percent of patients. They performed TAVR via the femoral artery in 94.7 percent of cases.

At 30 days post-TAVR, major adverse cardiac and cerebrovascular events occurred in 7.3 percent of patients in the test and safety groups and 9.9 percent of patients in the control group. The study was not powered for clinical outcomes, according to Kodali, but he said the difference was not statistically significant. The researchers defined major adverse cardiac and cerebrovascular events as all-cause death, stroke and stage 3 acute kidney injury.

Meanwhile, strokes occurred in 5.6 percent and 9.1 percent of patients, respectively, which was also not a statistically significant difference. Only one patient had a vascular complication related to the filter.

The median total new lesion volume in protected territories was 42 percent lower in the Sentinel groups compared with the control group (102.8 mm3 vs. 178.0 mm3). That difference was not statistically significant, either.

The Sentinel captured debris in 99 percent of patients. Nearly half of patients had valve tissue or calcification captured in the filter.

A post-hoc multivariable analysis found that preexisting lesion volume and valve type were predictors of new lesion volume.

“There are important lessons from this trial, which should impact future research on neuroprotection during TAVR,” the researchers wrote. “In particular, the use of quantitative MRI analyses as a surrogate endpoint must be further clarified, including stricter time windows for follow-up studies and more accurate assumptions of expected control arm results, such that sample sizes can be adjusted appropriately. The requirement of baseline MRI studies to account for prior lesion volume and the need to adjust for differences in valve type (e.g. stratification of valve types during randomization) cannot be overemphasized.”