Protembis Gets FDA Approval for Cerebral Protection Device IDE; Study Design Could Show Superiority to Boston Scientific’s Sentinel Device

Protembis GmbH, a cardiovascular medical device company headquartered in Germany, has received the FDA’s approval of its pivotal Investigational Device Exemption (IDE) trial for the PROTEMBO Cerebral Embolic Protection (CEP) System. This device is designed to provide comprehensive cerebral artery protection during transcatheter aortic valve replacement (TAVR) procedures. It would potentially compete against Boston Scientific’s Sentinel device for cerebral embolic protection in the U.S. which was approved by the FDA in 2017. Additionally, Keystone Heart has CE Mark for their TriGUARD device.

The ProtEmbo System is an intra-aortic filter device that has been meticulously designed to safeguard the entire brain from embolic material released during TAVR procedures. It offers a low-profile, non-thrombogenic solution that provides protection for all cerebral vessels. Delivered through the left radial artery, this approach ensures optimal placement and stability while avoiding interference with TAVR equipment typically delivered through the femoral artery.

The PROTEMBO Pivotal IDE Trial is set to enroll between 250 and 500 randomized patients undergoing TAVR across the United States and Europe. The trial’s approach aims to demonstrate the superiority of the next-generation ProtEmbo CEP System over the current standard of care. It will utilize a hybrid control group, with half of the participants receiving no cerebral embolic protection (CEP), while the other half will receive the Sentinel CEP by Boston Scientific, which covers only two of the three cerebral arteries originating from the aortic arch.

A key focus of the trial is its unique adaptive superiority trial design, which incorporates an innovative statistical approach. This design allows for pre-specified interim analyses and the potential for early termination in the event of demonstrating superiority. The primary efficacy endpoint for this trial will be assessed through diffusion-weighted magnetic resonance imaging (DW-MRI). Additionally, the primary safety endpoint will evaluate the rate of major adverse cardiac and cerebrovascular events (MACCE) within 30 days, with neurological events being adjudicated by stroke neurologists.

The significance of this trial is underscored by its distinct focus on evaluating the next generation of CEP technology compared to the current standard of care. Dr. Roxana Mehran, Chair of the Study Executive Committee at Mount Sinai in New York, expressed her enthusiasm for this landmark trial, emphasizing its unique design and the potential for the next generation CEP technology to outperform current methods.

In late 2022 Protembis completed its PROTEMBO C Trial for CE Mark registration. In this single-arm study conducted at eight European centers, 41 patients were enrolled. The primary safety endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCE), as defined by VARC 2, at 30 days. The primary performance endpoint was the composite rate of technical success compared to predefined performance goals (PG). Secondary endpoints included brain diffusion-weighted magnetic resonance imaging (DW-MRI), new lesion volume, and the rate of death or all strokes compared to historical data. Results from the study showed that 37 out of the 41 enrolled patients underwent TAVI with the ProtEmbo device, representing the intention-to-treat (ITT) population. Both primary endpoints were successfully met. The MACCE rate at 30 days was 8.1%, with the upper limit of the 95% confidence interval (CI) at 21.3%, compared to the PG of 25% (p=0.009). The technical success rate was 94.6%, with the lower limit of the 95% CI at 82.3%, surpassing the PG of 75% (p=0.003). Importantly, the new DW-MRI lesion volumes observed with ProtEmbo were smaller than those reported in historical data. Furthermore, 87% of patients who underwent MRI follow-up had no single lesion exceeding 150 mm3. Only one stroke occurred in a patient in whom the device was removed prematurely before the completion of the TAVI procedure.