Vdyne Granted FDA IDE For Tricuspid Valve Replacement Study

The FDA granted an investigational device exemption (IDE) to Vdyne for their tricuspid valve replacement (TTVR) device allowing them to proceed with a pivotal clinical trial of a transcatheter tricuspid valve replacement (TTVR) for the treatment of severe tricuspid regurgitation. Severe tricuspid regurgitation affects over 1.5 million people in the U.S. alone and the majority of these patients are not treated for their tricuspid regurgitation due to the high mortality for traditional open-heart surgery.

The Importance of Innovation

FDA Grants Investigational Device Exemption for Vdyne’s Tricuspid Valve System. Vdyne announced that the U.S. Food and Drug Administration (FDA) has granted an Investigational Device Exemption (IDE) for the early clinical investigation of its tricuspid valve system, VD-01, a transcatheter tricuspid valve replacement (TTVR) system. The pivotal randomized controlled trial, TRIVITA, will be conducted in the US and will enroll approximately 730 patients with severe tricuspid regurgitation. Severe tricuspid regurgitation (TR) affects over 1.5 million people in the U.S. alone and the majority of these patients are not currently treated for their condition due to high risk of mortality with open heart surgery.

Why It Matters

Severe tricuspid regurgitation (TR) – Severe tricuspid regurgitation are three words that describe a condition that has long sat in the shadow of left-sided valve disease. For years, cardiologists treated tricuspid problems as secondary or too risky for surgery. That is changing. More patients are being identified, and a growing number are not good candidates for traditional open-heart surgery. A new, less invasive replacement option tested in a rigorous U.S. trial could widen treatment choices and change outcomes for patients with advanced disease.

Intricacies of Devices

Engineers and inventors developing a TTVR must first realize that transfemoral catheter-based therapies delivered via small incisions and imaged open have been highly successful treating aortic and mitral valvular disease. Tricuspid valvular disease, however, is a right-sided heart problem that poses unique challenges due to the high degree of anatomical variability found among tricuspid valves and their surrounding cardiac structures. In particular, tricuspid free standing valve leaflets and surrounding cardiac structures are very thin and are therefore very friable. Pre-existing cardiac pacemaker leads as well as ICD leads often cross over the tricuspid valve and present additional problems for the design and use of such a device. Even imaging of the tricuspid valve can pose challenges, as do the management of various tricuspid anatomies. A tricuspid replacement valve, therefore, must be engineered to handle a wide degree of tricuspid valve and cardiac anatomy while minimizing additional risk to the patient. This is an important engineering challenge that needs to be met.

What’s Still Needed

But the FDA’s grant of an IDE to a device and the subsequent conduct of a U.S. pivotal clinical trial are far from a guarantee of widespread use of that device. The FDA in the IDE application and in approval of the study will specify criteria for determination of safety for patients in the study and for demonstration of clinical benefit to patients in the study. The heart team of clinicians will judge in the postmarket setting the clinical results of interest (e.g., symptom relief and functional improvement), as well as information regarding the duration of time that clinical results are achieved, and the incidence of reintervention of any type. These same clinicians will also determine how well the device is engineered to safely treat a broad array of patients with TR of varying etiologies and degrees of complexity of right heart anatomy as well as earlier stages of tricuspid valve disease.

What the Research Says

TRIVITA Trial. Vdyne’s tricuspid valve replacement device will be compared against Edwards EVOQUE TTVR in a prospective, randomized controlled study of approximately 730 patients across 60 centers in the U.S. and Europe. Severe tricuspid regurgitation patients who are symptomatic and on optimal medical therapy for heart failure with NYHA functional classification of II, III or IV will be enrolled. The study will demonstrate safety and efficacy of the VD-01 TTVR device as a less invasive alternative to open heart surgery for these patients. A single arm registry will be used to follow additional patients with severe tricuspid regurgitation who are not candidates for the Edwards EVOQUE TTVR due to high risk of procedural complications.

Engineering for Complex Anatomy

The VD-01 tricuspid valve replacement system has several key technical differentiators that allow for treatment of the asymmetric morphology of the tricuspid valve.

• Asymmetric Frame: A nitinol dual-frame structure designed to fit an annular perimeter of up to 180 mm without requiring extensive native leaflet support.
• Repositionability: Unlike some fixed systems, the Vdyne valve is fully retrievable and repositionable before final release, allowing clinicians to optimize placement in real-time.
• Minimal Imaging Burden: The system utilizes a proprietary side-delivery technology that aims to reduce the heavy reliance on complex echocardiography during the procedure, potentially shortening operative times.
• Ventricular Relief: A “pop-off” aperture can be used to allow mild residual regurgitation, preventing sudden ventricular afterload mismatch after the valve is replaced.

Who It Affects

Clinical Significance and Market Impact

Preliminary results from the first Vdyne VD-01 implants performed on an investigative basis or as part of early feasibility research have been nothing short of spectacular. In each and every case, the severe TR was eliminated and there was a significant improvement in Functional Status with an attendant increase in exercise capacity as measured by increased distance that a patient can walk prior to Shortness of Breath. It is expected that the results from the TRIVITA study will be used to assess the safety of the VD-01 device over the long term and to compare its performance to other commercially available TTVR products for the treatment of patients with severe, symptomatic TR who are at high risk of operative morbidity and mortality due to their fragile anatomy or prior cardiac surgery including presence of one or more prior implanted pacemaker leads.

Patients

The patients who could potentially benefit from this emerging technology are generally of an older age and suffering from other cardiac problems that may cause them to become fatigued. Other symptoms that these patients could be experiencing are an increase in weight due to fluid retention that has leaked into their body’s tissues and/or organs and frequent visits to and from the hospital for treatment of various health problems. These patients are too ill for an open heart surgical procedure and would be considered candidates for a transcatheter tricuspid valve replacement tested in a pivotal U.S. trial for patients with severe tricuspid regurgitation who are symptomatic on medical therapy and at high risk for surgery.

Cardiologists and Cardiac Surgeons

Interventional Cardiologists who intend to perform the implantation of the transcatheter tricuspid valve replacement will need to familiarize themselves with the variety of tricuspid valve anatomies and learn how to deploy the appropriate valve in each of these cases. In addition to the Interventional Cardiologists, the Cardiac Surgeons will also be impacted as they will be able to manage potential and actual complications that may arise during the procedure. The hybrid approach will also need to be managed by the cardiac surgeons. The Imaging Specialists (Echocardiographers and Cardiac CT and MRI technologists) will also be impacted by the implanted device and its related structures as these will require increased imaging to properly assess the positioning and function of the device. Similar to other structural heart interventions, the amount of required imaging will be put to test.

Hospitals and Healthsystems

The challenge for the hospitals and healthsystems will be to develop programs for interventions of the structural heart. From an operational and financial point of view decisions have to be made based on the clinical data of said interventions. Are the interventions save to be performed in a certain hospital? Are they cost effective compared to the treatment of heart failure as it is today? Are there even savings in the long run due to avoided admissions for heart failure? The payers as well as the policy makers will look at the same clinical data to make a decision for reimbursement of such a device.

Caregivers and Families

The many patients with significant tricuspid regurgitation are generally older individuals with other significant heart disease. As a result, they are often tired, have significant amounts of fluid, and have multiple admissions for various reasons. A transcatheter tricuspid valve replacement, such as the one currently being tested in the TRIVITA trial and now the pivotal U.S. IDE trial, would be primarily for the treatment of the symptomatic patient with severe tricuspid regurgitation at high risk for surgery, who has been optimized on medical therapy.

What Changes

• Clinical trials will move from first-in-human feasibility work to a larger, pivotal study in the United States. That means more patients will get access to the device under protocol, and the field will get higher-quality evidence on safety and effectiveness.
• Heart teams and structural heart programs will need to prepare for new training and planning. Operators will learn device-specific techniques for side-delivery and repositioning, and imaging teams will refine protocols to support implantation and patient selection.
• Device features that reduce the need for extensive imaging or that allow retrieval and repositioning could lower procedural risk in complex anatomy. If those claims hold up, clinicians may treat patients who were previously considered untreatable with transcatheter options.
• Payers and hospitals will face early decisions about coverage and capacity. Evidence from the pivotal trial will shape reimbursement and whether the therapy becomes broadly accessible beyond specialized centers.

Nuances in Innovation

As TRV replacement technology advances and becomes more refined, it will be important for the heart team to develop nuances to transfer this technology to other centers. This will not be an easy task given the complexity of TRV interventions. Many of the early compassionate use and feasibility studies have been conducted in high volume centers by experienced operators. Currently, there are training programs and proctorship opportunities available to help facilitate the replication of these results in other centers. It will also be important for long-term follow-up to determine the long-term performance of valves in the tricuspid position. The pressures on the right side of the heart as well as the presence of devices such as pacemaker leads alter the mechanical environment of the tricuspid valve. As such, it will be important for clinicians to understand the long-term results for TRV replacement as well as the potential need for future interventions, i.e. valve in valve strategy.

Patient Selection

An additional benefit of early intervention with a patient tailored tricuspid valve replacement would be the potential to prevent tricuspid regurgitation from progressing to more severe stages of heart failure and to prevent some of the complications of heart failure. The safety of the replacement procedure for patients who are treated on an urgent basis will be a critical factor in the determination of the timing of the intervention. The clinical status of the patient will also be a critical factor in the determination of the appropriate time for intervention. For the TRIVITA trial’s pivotal study in the U.S., the information from the studies of compassionate use and feasibility will be used to determine the study’s inclusion and exclusion criteria as well as the endpoints to measure the results of the study. Thus, the results of the TRIVITA trial will provide important insights to the medical community on the patient selection criteria for the replacement of failing native tricuspid valves in patients who are at high risk for operative mortality. The results of the studies of compassionate use will determine a very conservative approach to the treatment of patients who would benefit from earlier intervention.

A Growing Market

This area of structural heart intervention is expected to become very competitive very quickly as a number of technologies are expected to be ready to begin pivotal studies for transcatheter tricuspid valve replacements in the near future for both tricuspid failure and prior tricuspid surgery failure. In terms of key features and potential advantages and disadvantages for each technology, one of the largest differences will be the amount of imaging that will be required for the different devices.

Looking Ahead

The TRIVITA trial is a FDA IDE approved pivotal study for a Class II medical device. Assuming the trial meets its endpoints the device approved for marketing and sale as a Class II medical device will hopefully offer an improved therapeutic option for the management of patients with severe, symptomatic tricuspid regurgitation. The success of this and similar future devices for the treatment of tricuspid regurgitation will have a profound impact on the management of heart failure and on the clinical practice guidelines for the management of patients with structural heart disease. Its implementation will require significant changes in the organization of programs for the delivery of structural heart interventions, for reimbursement of expensive interventional devices, and for patient access to these devices and their related interventions. In the long run it will be important to study the reduction in hospital readmissions, the improvement in functional status and the cost savings for the patient and the health care system for which these devices and their related interventions are indicated.

In the interim, we must recognize that the receipt of an IDE to support the conduct of a pivotal trial represents an important regulatory milestone; however, significant work remains to be accomplished. All practitioners and programs will need to keep a very close eye on the results of the TRIVITA trial; in anticipation of being able to teach and provide the appropriate care to selected individual patients.

References

1. https://www.massdevice.com/vdyne-fda-ide-tricuspid-valve-replacement/
2. https://clinicaltrials.gov/study/NCT05797519