The prospects of TMVR devices rely on careful endpoint measurement and enrollment.
Transcatheter aortic valve replacement (TAVR) is one of the most significant cardiovascular scientific advancements of the past decade, but its sister procedure, transcatheter mitral valve replacement (TMVR), has not seen the same success. TMVR devices have faced a number of challenges, which have thus far prevented any devices from making it to market.
The obstacles to approval, however, are not insurmountable. The success of TAVR has led to disappointment over the comparatively lackluster progress of TMVR, but there remains a robust market and future hope for clinically safe and effective TMVR devices.
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There is a significant market for TAVR. Forty percent of aortic valve stenosis patients are deemed too high risk for traditional open heart surgery. As a result, 100,000 people in North America and 190,000 people in Europe are candidates to undergo this procedure.
The TMVR market is even larger; 2-3% of the global population experiences mitral valve regurgitation (leakage). Despite the number of cases, only 70,000 people in the United States undergo mitral valve surgery each year. But whereas patients requiring aortic valve replacement are typically older people with aortic valve stenosis, mitral valve patients can suffer from a variety of conditions. Further complicating the problem is the fact that mitral valve structure is complex and subject to significant individual differences.
Key Challenges to TMVR Device Development
Mixed patient populations, the complex structure of the mitral valve, and the numerous causes of mitral valve regurgitation all contribute to the challenge of developing safe and effective TMVR devices.
In addition, mitral valve regurgitation is comorbid with a variety of other conditions: Atrial fibrillation, coronary artery disease, other valvular conditions, and other congenital anomalies. These conditions may create challenges for device development and patient enrollment in clinical trials.
Other obstacle can include the complexity of patient populations and the currently high-risk nature of the treatment, which can complicate selection and measurement for clinical trials.
The Path to TMVR Approval
The path to approval of TMVR devices, therefore, will require careful enrollment and endpoint measurement. The Mitral Valve Academic Research Consortium (MVARC) recommends the following in enrolling patients:
- Inclusion criteria stratify patients with primary and secondary mitral valve regurgitation
- Pre-specified assessments should be used as enrollment factors, including patient frailty, major organ system compromise or procedure-specific impediments
- A heart team should evaluate all potential trial participants
- Local principal investigators should present candidates to a central trial eligibility committee
- Sites must include principal investigators and teams with significant mitral valve replacement experience
In addition to patient enrollment best practices, MVARC recommends defining standard clinical endpoints for TMVR trials:
- Neurological events
- Myocardial infarction
- Access and vascular complications
- Bleeding complications
- Acute kidney injury
- Arrhythmias and conduction system disturbances
- Device and procedural success and specific device-related technical failure issues and complications as well as secondary endpoints involving quality-of-life measures
- Functional performance and echocardiographic assessments including residual MR and perivalvular leaks
Although the mitral valve is mere millimeters from the aortic valve, transcatheter mitral valve replacement is still years away. Fortunately, TMVR device makers are using a variety of approaches, which hopefully increase the odds of success. As of fall 2016 there were at least eight TMVR devices in trial, a promising sign for the future of the technology. Careful attention to enrollment and endpoint strategies are the next steps to move these devices closer to market.
David Novotny is senior vice president of the Medical Device & Diagnostic Division at Novella Clinical. He has more than 18 years of clinical research experience in hospital, CRO, medical device, and biopharma environments.
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