Multicenter Trial Launched to Evaluate New LVAD Option for Advanced Heart Failure

The first U.S. clinical trial is underway to test the safety and efficacy of the BrioVAD System — an alternative to the HeartMate 3 (HM3), which is currently the only durable left ventricular assist device (LVAD) option available for advanced heart failure in the United States. BrioVAD has fully magnetically levitated pump technology and new features designed to reduce complications and potentially improve the patient experience.

The trial, INNOVATE (Investigation of a Novel Magnetically Levitated VAD for the Treatment of Refractory Left Ventricular Heart Failure; NCT06310031), is now conducting safety assessment of the investigational device at eight centers, including Cleveland Clinic, with short- and long-term efficacy evaluation compared with HM3 soon to follow.

“BrioVAD has the potential to offer patients more options when it comes to LVAD therapy,” says Pavan Bhat, MD, INNOVATE’s Cleveland Clinic site principal medical investigator and a cardiologist in the Section of Heart Failure and Cardiac Transplantation. “Having another device available would be instrumental in driving more competition and innovation.”

Recent plateauing of LVAD evolution

Fueled by intense competition among manufacturers, significant advances in mechanical circulatory support have been made over the past three decades. Bulky pulsatile flow devices have been replaced by the current HM3, a fully magnetically levitated continuous-flow pump. Changes have been accompanied by major reductions in stroke rates (now about 2% a year beyond 30 days after implant) and device durability, to the point that failure is now rare.

The MOMENTUM 3 trial established the superiority of HM3 over the HeartMate II axial continuous-flow pump in 2018, and the HeartWare centrifugal continuous-flow pump was withdrawn from the market for safety reasons in 2021. Since then, HM3 has been the only commercially available LVAD option in the U.S., and the field has not seen much innovation since it was first implanted in 2017.

BrioVAD’s new design features

BrioVAD incorporates a number of designs aimed at reducing complications and improving the user interface. They include:

• A centrifugal totally magnetically levitated long blade rotor, which creates a low-turbulence blood flow path designed to minimize shear stress to enhance hemocompatibility.
• Lower pump weight and profile, which may be an advantage for implanting in smaller patients and when using a thoracotomy approach.
• Fewer and more flexible leads and lighter peripheral components, potentially improving patient comfort and reducing risk of driveline infection.

The first in-human implant of the BrioVAD was performed in 2017, and more than 350 patients have had the device implanted outside the U.S., primarily in China.

INNOVATE in brief

After INNOVATE’s safety phase is complete in a cohort of 45 patients, the trial will open to more centers for the staged pivotal study, enrolling an expected 237 patients for a short-term cohort (followed until six months after implant) and then continuing and expanding to more than 400 patients in a long-term cohort to be followed for 24 months.

As the highest-volume U.S. center for LVAD implants over the past five-year period, Cleveland Clinic is expected to be one of the highest enrollers of patients in the trial “because we want to bring the best available technology to our patients,” says Michael Tong, MD, Director of Cardiac Transplantation and Mechanical Circulatory Support, who serves as surgical principal investigator for INNOVATE at Cleveland Clinic. He notes that Cleveland Clinic performed its first BrioVAD implantation for the trial in late April.

Trial participants are being randomized 2:1 to BrioVAD versus HM3 across all phases of the study. Treatment is nonblinded.

The primary endpoint is a composite of survival to transplantation, cardiac recovery, or six months (24 months in the study’s long-term phase) of LVAD support free from debilitating stroke or reoperation to replace the pump. This endpoint will be evaluated to assess for noninferiority.

Secondary outcomes account for adverse events and days spent in a hospital, skilled nursing facility or inpatient rehabilitation. Functional status, stroke-related disability and quality of life will also be evaluated.

“We are especially interested in the complications of stroke, bleeding, infection and device failure,” Dr. Tong explains. “With HM3, rates of stroke and device failure are already extremely low, so we hope BrioVAD can match this record. In addition, we’ll see whether the design improvements offer a reduction in infections, due to a more flexible driveline, which can decrease days spent in hospital after implantation.”

Dr. Bhat adds that the bar is relatively high for safety and efficacy outcomes in INNOVATE, with inclusion criteria similar to those in MOMENTUM 3 and rather reflective of contemporary clinical practice for durable LVAD therapy.

Opportunity to revive advancements in LVAD tech

“LVADs have advanced to the point that they are not just lifesaving but also provide excellent quality of life,” Dr. Bhat says. Dr. Tong concurs, noting that LVADs now offer such good durability that they are becoming an excellent alternative to heart transplant with equivalent survival in many patient groups.

Despite currently excellent outcomes with HM3, both Drs. Tong and Bhat want to see the stage set for advancements in LVADs to expand device options, further improve survival, reduce complications and improve the patient experience.

“For instance,” Dr. Tong says, “we’re hopeful that the next generations of LVADs will be much more efficient in battery usage, which can lead to even smaller peripherals and the ability to be untethered to batteries for periods of time. Imagine that the only thing a patient needed to carry around would be a small computer the size of a smartphone that could even be disconnected for a few hours to allow for more physical activity. That reality may be only a few years away.”

“We hope that INNOVATE will lead to a new option for patients with severe heart failure,” Dr. Bhat concludes. “Most importantly, I expect that it will help advance the field, encouraging competition and new developments.”

Dr. Tong reports receiving speaking honoraria and having done consulting work for Abbott, which markets the HM3. Dr. Bhat reports no financial relationships relevant to the INNOVATE trial.