Transcatheter Mitral Valve Replacement for Mitral Valve Regurgitation

Not currently recruiting at 26 trial locations

Overseen By Sarah Brown

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medtronic Cardiovascular

Disqualifiers: Prior valve surgery, Stroke, Myocardial infarction, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device for individuals with severe mitral valve regurgitation, a condition where the heart's mitral valve doesn't close tightly, causing blood to flow backward. The goal is to determine if the Twelve TMVR System, a transcatheter mitral valve replacement device, is safe and effective for those with serious symptoms. Individuals who frequently experience fatigue or difficulty breathing due to severe mitral valve issues might be suitable candidates. The study uses a less invasive approach with the device, which could benefit those at very high risk for traditional surgery. As an unphased trial, it offers patients access to innovative treatment options that could enhance their quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the Twelve TMVR System is safe for mitral valve regurgitation patients?

Research has shown that the Twelve TMVR Implant, used to treat mitral valve regurgitation (when the heart's mitral valve doesn't close properly), has undergone safety testing. In one study with 50 patients, about 14% did not survive 30 days after the procedure. However, the procedure succeeded in 98% of cases, meaning the device was placed correctly and functioned as intended.

Another study followed patients for two years and found that the device was successfully implanted in 97% of them. During this period, 39% of patients passed away from various causes. It's important to note that these patients were already at high risk due to their severe heart condition.

Serious problems like heart attacks or major strokes were rare. Only 0.6% experienced a heart attack, and 3.1% had a major stroke within two years. This suggests that while risks exist, serious complications are uncommon.

These findings provide insights into the safety of the Twelve TMVR Implant. However, anyone considering participation in a trial should discuss all potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for mitral valve regurgitation, which often involve open-heart surgery or medication to manage symptoms, the Twelve TMVR Implant offers a less invasive alternative. This treatment is unique because it uses a transcatheter approach to replace the mitral valve, significantly reducing the need for a large surgical incision. Researchers are excited about this option because it can potentially offer quicker recovery times and fewer complications compared to open-heart surgery, making it a promising option for patients who are high-risk surgical candidates.

What evidence suggests that the Twelve TMVR Implant is effective for mitral valve regurgitation?

Research has shown that the Twelve TMVR Implant, which participants in this trial will receive, effectively treats mitral valve regurgitation, a condition where the heart's mitral valve doesn't close tightly. In a study with 50 patients, the procedure succeeded 98% of the time, usually working on the first try. Most patients experienced little to no remaining mitral valve leakage after treatment. Another study found that the procedure was technically successful and effectively reduced mitral valve leakage. Additionally, patients who underwent this procedure often spent less time in the hospital compared to those who had traditional surgery. These findings suggest that the Twelve TMVR Implant could be a promising option for people with severe mitral valve regurgitation. ^{2 5 6 7 8}

Who Is on the Research Team?

Lynnett Stahl

Principal Investigator

Medtronic

Are You a Good Fit for This Trial?

This trial is for very high-risk patients with severe, symptomatic mitral valve regurgitation (MR Grade 3-4+), specifically those who can undergo a transcatheter procedure. Participants must have a heart structure that fits the TMVR system and not have had recent strokes, heart attacks, or other valve surgeries.

Inclusion Criteria

Your doctor thinks it's possible to access your heart through the chest (for PILOT study only).

I have severe leakage in my heart's mitral valve.

Your mitral valve is the right shape and size for the Twelve TMVR/Intrepid device.

Exclusion Criteria

My kidney function is impaired with high creatinine levels.

I have had or need surgery for a heart valve problem.

There is something abnormal in your heart that could cause a blockage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Transcatheter Mitral Valve Replacement (TMVR) implant

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Twelve TMVR Implant

Trial Overview The study tests two versions of the Medtronic Intrepid™ Transcatheter Mitral Valve Replacement System: one via trans-apical access (PILOT) and another through transfemoral transseptal access (EFS). It aims to assess their safety and performance in treating severe mitral regurgitation.

How Is the Trial Designed?

Group I: Transcatheter Mitral Valve Replacement (TMVR) Implant Experimental Treatment 2 Interventions

Twelve TMVR Implant

Who Is Running the Clinical Trial?

Medtronic Cardiovascular

Lead Sponsor

Trials

78

Recruited

37,300+

Geoff Martha

Medtronic Cardiovascular

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Kendra J. Grubb

Medtronic Cardiovascular

Chief Medical Officer

MD from Emory University

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

In a study of five high-risk patients undergoing transcatheter mitral valve replacement (TMVR) with the Tendyne device, most patients showed significant improvement in symptoms and exercise capacity after 18 months to two years, indicating the device's efficacy.

Despite some complications, the Tendyne device demonstrated stability and good hemodynamic function, with no new paravalvular leaks or late migration observed in surviving patients, suggesting a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter mitral valve replacement: long-term outcomes of first-in-man experience with an apically tethered device- a case series from a single centre. Duncan, A., Daqa, A., Yeh, J., et al.[2022]

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]

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 (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]

Transcatheter mitral valve replacement (TMVR) offers a promising solution for completely eliminating mitral regurgitation (MR), which is a significant advantage over less certain transcatheter repair methods like TEER.

The authors emphasize the importance of conducting randomized controlled trials (RCTs) to thoroughly evaluate the safety and effectiveness of TMVR compared to existing treatments, as well as to inform clinical practices and reimbursement policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trials Are Needed for Transcatheter Mitral Valve Replacement. Rogers, JH., Sorajja, P., Thourani, VH., et al.[2021]

Transcatheter mitral valve repair (TMVR) is a safer option than surgical mitral valve repair (SMVR) for older patients and those with more comorbidities, showing lower rates of complications such as permanent pacemaker implantation and major bleeding.

Despite being older and having higher comorbidity scores, TMVR patients experienced shorter hospital stays and were less likely to be discharged to skilled nursing facilities compared to those undergoing SMVR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes. Jogu, HR., Arora, S., Strassle, PD., et al.[2021]

Transcatheter mitral valve repair (TMVR) using the MitraClip system was successfully performed on 3 Chinese patients with severe mitral regurgitation, showing significant improvements in heart function and pressure measurements post-procedure.

All patients experienced a reduction in heart chamber sizes and NT-ProBNP levels, indicating improved heart function, with no complications reported, suggesting that TMVR is a safe and effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Initial experience of treating patients with severe mitral regurgitation with transcatheter mitral valve edge-to-edge repair in China]. Ge, JB., Zhou, DX., Pan, WZ., et al.[2013]

Transcatheter mitral valve replacement (TMVR) in high-surgical-risk patients with severe mitral regurgitation showed significant improvements, with 93.2% of surviving patients having no mitral regurgitation at 2 years and a reduction in heart failure hospitalizations from 1.30 to 0.51 events per year post-procedure.

While the all-cause mortality rate was 39% over 2 years, with a notable 43.6% of deaths occurring within the first 90 days, the procedure led to sustained symptom improvement, with 81.6% of patients reporting NYHA functional class I or II at 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Symptomatic Mitral Regurgitation. Muller, DWM., Sorajja, P., Duncan, A., et al.[2022]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02322840

Transcatheter Mitral Valve Replacement System (TMVR ... The study is pilot trial to evaluate the safety and performance of the Twelve TMVR System in very high risk mitral regurgitation patients. EFS: The study is ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.125.015298

TMVR for the Treatment of Mitral Regurgitation: A State-of- ... In the first pilot trial (50 patients), the 30-day mortality rate was 14%, with a procedural success rate of 98% and mild or no residual MR ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7262433/

Outcomes of open mitral valve replacement versus ... Patients undergoing TMVR were older and more financially affluent. TMVR was more costly but was associated with a shorter hospital stay and similar mortality ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2474870625002945

Transcatheter Mitral Valve Replacement Using ... Transcatheter mitral valve replacement (TMVR) using dedicated devices is associated with high rates of technical success and effective mitral regurgitation (MR) ...

5. eurointervention.pcronline.com eurointervention.pcronline.com/article/clinical-outcomes-of-transcatheter-mitral-valve-replacement-two-year-results-of-the-choice-mi-registry

Clinical outcomes of transcatheter mitral valve replacement This study analyzed outcomes of 400 patients undergoing TMVR with different devices from the international CHOICE-MI Registry, finding procedural success, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02428010

Twelve Transcatheter Mitral Valve Replacement (TMVR ... The study is a prospective, multi-center, non-randomized trial to evaluate the safety and performance of the Twelve TMVR System in very high risk patients with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34736561/

2-Year Outcomes of Transcatheter Mitral Valve ... Prostheses were successfully implanted in 97 (97.0%) patients. At 2 years, all-cause mortality was 39.0%; 17 (43.6%) of 39 deaths occurred ...

8. jacc.org jacc.org/doi/10.1016/j.jcin.2023.09.003

The HighLife TSMVR Feasibility Study The 1-year results from the HighLife TSMVR feasibility study demonstrate a high technical success rate, excellent valve function, no left ventricular outflow ...