Transcatheter Mitral Valve Replacement for Mitral Valve Regurgitation

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: HighLife SAS

Must be taking: GDMT

Disqualifiers: Mitral stenosis, Rheumatic valve disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Study to evaluate the feasibility, safety and performance of the HighLife trans-septal Transcatheter Mitral Valve in patients with moderate-severe and severe mitral regurgitation who are at high risk for surgical treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must be on maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months before participating.

What data supports the idea that Transcatheter Mitral Valve Replacement for Mitral Valve Regurgitation is an effective treatment?

The available research shows that Transcatheter Mitral Valve Replacement (TMVR) is a new treatment option for severe mitral regurgitation, especially for patients who are not suitable for traditional surgery due to other health issues or advanced age. Although the worldwide experience is limited to fewer than 200 cases, TMVR has been successfully used in patients with specific conditions like degenerative mitral stenosis and failed mitral bioprosthesis. However, the high rate of complications within 30 days after the procedure suggests that more improvements and studies are needed to confirm its effectiveness. Compared to surgical valve replacement, TMVR offers a less invasive option for high-risk patients, but it still requires further development to ensure safety and effectiveness. ^{1 2 3 4 5}

What safety data exists for the HighLife Transcatheter Mitral Valve Replacement System?

A study conducted at West China Hospital evaluated the safety and feasibility of the HighLife transseptal mitral valve replacement (TSMVR) system in high-risk patients with severe mitral regurgitation. The study included four patients and reported technical success in all cases, with no residual mitral regurgitation, paravalvular leakage, or left ventricular outflow tract obstruction. However, three major cardiovascular and cerebrovascular adverse events occurred within 30 days, including ventricular tachycardia, iatrogenic atrial septal defect closure, and heart failure readmission. The study suggests that the HighLife system is feasible and relatively safe for this patient group. ^{6 7 8 9 10}

Is the HighLife Transcatheter Mitral Valve Replacement System a promising treatment for mitral valve regurgitation?

Yes, the HighLife Transcatheter Mitral Valve Replacement System is a promising treatment for mitral valve regurgitation. It offers an alternative to surgery for patients who are at high risk, providing a new option for those with severe symptoms. This treatment is part of a rapidly evolving field, showing potential in early clinical experiences. ^{1 4 8 11 12}

Eligibility Criteria

This trial is for adults over 18 with moderate to severe mitral valve regurgitation who are at high risk for surgery. Candidates must have been on medical therapy for a month, be in NYHA Functional Class II-IV, and meet specific anatomical criteria. Exclusions include recent stroke/TIA, severe carotid stenosis, pregnancy, inability to follow up or take blood thinners, recent pacemaker implantation, active infections or ulcers.

Inclusion Criteria

I am willing to join the study and have signed the consent form.

You are at a high risk for open-heart surgery based on evaluations from a team of heart doctors, considering other health problems, weakness, and difficulty performing daily activities.

I have some limitations on physical activity due to heart problems.

Exclusion Criteria

I have not had an active ulcer or GI bleeding in the last 3 months.

My doctor expects I have less than 12 months to live due to a non-heart related condition.

I cannot tolerate blood thinners or medications that prevent blood clots.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo the trans-septal mitral valve replacement procedure using the HighLife TSMVR system

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and performance of the HighLife TSMVR system at 30 days post-procedure

4 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and performance of the HighLife TSMVR system

6 months

Treatment Details

Interventions

• HighLife Transcatheter Mitral Valve Replacement System

Trial Overview The study tests the HighLife Transcatheter Mitral Valve Replacement System's safety and performance in patients with significant heart valve leakage who can't undergo standard surgery. It involves placing a new valve via catheter without open-heart surgery.

Participant Groups

Group I: Transcatheter Mitral Valve Replacement Experimental Treatment 1 Intervention

HighLife TMVR System is a novel and innovative approach developed as an alternative treatment for severe MR when medical treatment is maximal and surgical interventions not possible or at high risk. The HighLife TMVR system is composed of a Transcatheter Mitral Valve (TMV), a sub-annular implant (SAI), and their delivery systems and loading tools.

HighLife Transcatheter Mitral Valve Replacement System is already approved in European Union, United States for the following indications:

Approved in European Union as HighLife TSMVR for:

• Moderate-severe and severe mitral regurgitation in patients at high risk for surgical treatment

Approved in United States as HighLife TSMVR for:

• Moderate-severe and severe mitral regurgitation in patients at high risk for surgical treatment (under clinical investigation)

Who Is Running the Clinical Trial?

HighLife SAS

Lead Sponsor

Trials

5

Recruited

430+

Findings from Research

In a study of 25 patients with severe mitral regurgitation, 11 were successfully screened for transcatheter mitral valve replacement, demonstrating that this procedure can be a safe and effective treatment for well-selected patients, with no mortality reported in those treated with the Tendyne device.

Among the 14 patients who failed screening, alternative treatments such as the MitraClip procedure and open surgical repairs were successfully performed, indicating that there are viable options for patients who do not qualify for transcatheter replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-centre first experience with transapical transcatheter mitral valve replacement with an apical tether: factors influencing screening outcomes. Dahle, G., Helle-Valle, T., Beitnes, JO., et al.[2020]

The novel Cephea transcatheter mitral valve replacement system demonstrated excellent biological performance and safety in a preclinical model, with all 10 sheep surviving the study without complications and showing no signs of thrombosis or excessive calcification.

The transseptal delivery method was feasible and effective in pigs, with stable valve positioning and good hemodynamic profiles confirmed through echocardiography and autopsy, suggesting potential for future human applications in treating severe mitral regurgitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Evaluation of a Novel Percutaneous Transseptal Catheter-Based Mitral Valve Replacement Technology. Vahl, TP., Grogan, A., Cheng, Y., et al.[2020]

Transcatheter mitral valve replacement (TMVR) is a new treatment for severe mitral regurgitation, but it currently has a high 30-day mortality rate exceeding 30%, indicating significant risks associated with the procedure.

Despite its challenges, TMVR has shown promise in treating patients with degenerative mitral stenosis and failed mitral repairs, leading to ongoing multicenter registries aimed at improving device design and understanding the procedure's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves. Sarkar, K., Reardon, MJ., Little, SH., et al.[2019]

In a study of the first 100 patients undergoing transcatheter mitral valve replacement (TMVR), the procedure demonstrated a high technical success rate of 96% and an acceptable safety profile, with no intraprocedural deaths and only one major complication.

At one year post-procedure, 72.4% of patients were alive, with significant improvements in heart function and quality of life, as evidenced by 88.5% of survivors achieving New York Heart Association class I/II status and notable enhancements in walking distance and cardiomyopathy questionnaire scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Feasibility Study of a New Transcatheter Mitral Prosthesis: The First 100 Patients. Sorajja, P., Moat, N., Badhwar, V., et al.[2020]

Transcatheter mitral valve replacement offers a promising alternative for high-risk patients with mitral regurgitation who are not suitable for traditional surgical valve replacement due to factors like advanced age or severe left ventricular dysfunction.

Recent advancements in transcatheter valve technology and data on their durability suggest that these devices could eventually be used in lower-risk populations, expanding treatment options for mitral valve disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spectrum of transcatheter mitral valve replacement devices. Dudiy, Y., Brownlee, A., Ruiz, CE.[2016]

The Mi-thos TMVR system was successfully implanted in all 10 high-risk patients with severe mitral regurgitation, demonstrating a 100% intraoperative success rate without any periprocedural mortality or major complications during the 30-day follow-up.

All patients showed no or trace mitral regurgitation after the procedure, indicating effective valve function, with a median mitral valve gradient of 2.0 mmHg, suggesting that the Mi-thos TMVR system is a safe and feasible option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience. Yang, Y., Chen, J., Dong, L., et al.[2023]

The study evaluated the feasibility and safety of transseptal transcatheter mitral valve replacement (TSMVR) in four patients with severe mitral regurgitation, achieving technical success with no residual regurgitation or major complications immediately after the procedure.

While the procedure was deemed relatively safe, three major cardiovascular events occurred within 30 days, indicating the need for careful monitoring and further research on long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and safety of transseptal transcatheter mitral valve replacement for severe mitral regurgitation]. Chen, F., Zhao, ZG., Yao, YJ., et al.[2023]

Transcatheter mitral valve replacement (TMVR) using a new self-expanding valve was successfully performed in 50 high-risk patients with symptomatic severe mitral regurgitation, achieving a high device implant success rate of 96%.

At a median follow-up of 173 days, 79% of patients showed significant improvement in their symptoms, with mild or no residual mitral regurgitation confirmed by echocardiography, indicating the procedure's efficacy in enhancing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience With New Transcatheter Mitral Valve Replacement. Bapat, V., Rajagopal, V., Meduri, C., et al.[2022]

A novel technique for transcatheter mitral valve replacement (TMVR) was successfully performed on three high-risk patients, involving the perforation and ballooning of the anterior mitral leaflet to prevent left ventricular outflow tract (LVOT) obstruction, achieving a 100% procedural success rate.

Intraoperative assessments showed no significant LVOT obstruction, indicating that this method may enhance the safety and efficacy of TMVR in patients who are not candidates for traditional surgical approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction (BATMAN): A novel technique for patients undergoing transcatheter mitral valve replacement. Helmy, T., Hui, DS., Smart, S., et al.[2020]

Repeat transcatheter mitral valve replacement (rTMVR) can lead to shorter ICU and hospital stays compared to repeat surgical mitral valve replacement (rSMVR), making it a potentially safer option for high-risk patients.

While rTMVR has a comparable mortality rate to rSMVR, it is associated with a higher risk of reoperations, indicating that careful patient selection is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Outcomes After Transcatheter Versus Surgical Repeat Mitral Valve Replacement. Arafat, AA., Zahra, AI., Alhossan, A., et al.[2023]

In a study of 400 high-risk patients with symptomatic mitral regurgitation undergoing transcatheter mitral valve replacement (TMVR), the procedure achieved a technical success rate of 95.2% and resulted in significant improvements in heart function over 2 years.

Despite the high success rate, the 2-year all-cause mortality rate was 38.1%, with chronic obstructive pulmonary disease and other health factors identified as predictors of mortality, highlighting the need for careful patient selection and management to enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of transcatheter mitral valve replacement: two-year results of the CHOICE-MI Registry. Ludwig, S., Perrin, N., Coisne, A., et al.[2023]

Transcatheter mitral valve replacement (TMVR) shows high procedural success in patients with severe mitral regurgitation who are at high surgical risk, indicating it could be a valuable alternative to traditional surgery.

Despite its promise, TMVR faces challenges such as potential left ventricular outflow tract obstruction and thrombotic risks, highlighting the need for further studies on long-term outcomes and optimal anticoagulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Catheter-based Mitral Valve Replacement. Rawish, E., Schmidt, T., Eitel, I., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Single-centre first experience with transapical transcatheter mitral valve replacement with an apical tether: factors influencing screening outcomes. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Experimental Evaluation of a Novel Percutaneous Transseptal Catheter-Based Mitral Valve Replacement Technology. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Initial Feasibility Study of a New Transcatheter Mitral Prosthesis: The First 100 Patients. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

The spectrum of transcatheter mitral valve replacement devices. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Feasibility and safety of transseptal transcatheter mitral valve replacement for severe mitral regurgitation]. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Early Experience With New Transcatheter Mitral Valve Replacement. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction (BATMAN): A novel technique for patients undergoing transcatheter mitral valve replacement. [2020]

10. Brazil pubmed.ncbi.nlm.nih.gov

Comparison of Outcomes After Transcatheter Versus Surgical Repeat Mitral Valve Replacement. [2023]

11. France pubmed.ncbi.nlm.nih.gov

Clinical outcomes of transcatheter mitral valve replacement: two-year results of the CHOICE-MI Registry. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Current Status of Catheter-based Mitral Valve Replacement. [2021]