TMVR for Mitral Valve Disease

(INTERLUDE Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Caisson Interventional LLC

Disqualifiers: Severe mitral stenosis, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Intra-operative

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called Transcatheter Mitral Valve Replacement (TMVR) for individuals with severe mitral regurgitation, a condition where the heart's mitral valve doesn't close tightly, causing blood to flow backward. Researchers seek to determine if this treatment is safe and effective for those experiencing symptoms like shortness of breath or fatigue, particularly if they cannot undergo regular heart surgery. Candidates suitable for this trial include those diagnosed with severe mitral regurgitation and at high risk for traditional heart surgery. As an unphased trial, this study provides an opportunity to explore a potentially life-changing treatment option for those with limited alternatives.

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 Transcatheter Mitral Valve Replacement system is safe for treating mitral regurgitation?

Research has shown that Transcatheter Mitral Valve Replacement (TMVR) is generally well-tolerated, though some risks exist. In one study, the procedure succeeded in 97% of patients. However, risks must be considered. Specifically, within the first 90 days after the procedure, 43.6% of deaths occurred out of a total 39% mortality rate observed over two years. Another study found low complication rates and effective reduction of mitral regurgitation, a condition where the heart's mitral valve doesn't close properly, causing blood to flow backward in the heart. Additionally, 30 days after the procedure, only 2.7% of patients died, and strokes occurred in 1.2% of cases.

Overall, while some risks are present, the treatment has shown promise in reducing symptoms with relatively low complication rates. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for mitral valve disease, which typically involve open-heart surgery, Transcatheter Mitral Valve Replacement (TMVR) offers a minimally invasive alternative. TMVR is unique because it allows doctors to replace a faulty mitral valve without the need for traditional surgery, reducing recovery time and risk, especially for patients at high surgical risk. Researchers are excited about TMVR because it uses the Caisson TMVR System, which is designed to be inserted through a catheter, offering a potentially safer and more efficient option for those who cannot undergo conventional surgery.

What evidence suggests that the Transcatheter Mitral Valve Replacement is effective for mitral regurgitation?

Research has shown that Transcatheter Mitral Valve Replacement (TMVR) is a promising treatment for mitral regurgitation, a condition where the heart's mitral valve doesn't close properly. One study found that TMVR succeeded in reducing mitral regurgitation to mild or none in 98% of patients. The benefits persisted for two years, with patients experiencing fewer hospital visits for heart failure and improved overall well-being. Another study reported a technical success rate of nearly 97% for TMVR. While some risks exist, the procedure has proven effective for many patients. Overall, TMVR is a strong option for those at high risk for traditional heart surgery. ^{1 2 6 7 8}

Who Is on the Research Team?

Mat Williams, M.D.

Principal Investigator

NYU Langone Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals at high risk for heart surgery with severe, symptomatic mitral regurgitation and classified as NYHA Class II-IVa. It's not suitable for those with excessive calcification of the mitral valve, severe right ventricular dysfunction, recent stroke or heart attack, or certain other heart conditions.

Inclusion Criteria

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

My heart condition limits my physical activity.

I am at high risk for heart surgery.

Exclusion Criteria

I have a blockage in the heart affecting blood flow.

I have not had a stroke in the last 90 days.

I have not had a stroke or heart attack in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients with symptomatic mitral regurgitation are treated with the Caisson Transcatheter Mitral Valve Replacement (TMVR) System

Intra-operative

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Transcatheter Mitral Valve Replacement

Trial Overview The study is evaluating a Transcatheter Mitral Valve Replacement (TMVR) system to treat severe mitral regurgitation. The goal is to determine how safe and effective this minimally invasive procedure is in improving heart function.

How Is the Trial Designed?

Group I: Transcatheter Mitral Valve Replacement Experimental Treatment 1 Intervention

Patients with symptomatic mitral regurgitation (garde 3 or 4), determined to be a high risk for cardiovascular surgery, will be treated with the Caisson Transcatheter Mitral Valve Replacement (TMVR) System

Who Is Running the Clinical Trial?

Caisson Interventional LLC

Lead Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

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) 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]

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 replacement (TMVR) is a viable option for high-risk patients with failed mitral bioprosthetic valves (valve-in-valve, ViV) and annuloplasty rings (valve-in-ring, ViR), showing acceptable technical success rates of 92.3%.

However, patients undergoing ViR had significantly higher rates of complications, including life-threatening bleeding and acute kidney injury, as well as a higher 1-year mortality rate (28.7% vs. 12.6% for ViV), indicating that ViR procedures may carry greater risks compared to ViV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve Replacement for Degenerated Bioprosthetic Valves and Failed Annuloplasty Rings. Yoon, SH., Whisenant, BK., Bleiziffer, S., 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]

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 promise but is currently limited by complications such as left ventricle outflow tract obstruction and major bleeding from the transapical approach, which is the most common method used.

Recent observational studies indicate that TMVR can be performed with acceptable safety and efficacy, suggesting that with improved device design and delivery systems, its adoption in clinical practice could increase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of adverse outcomes after transcatheter mitral valve replacement. Overtchouk, P., Piazza, N., Granada, JF., et al.[2019]

Transcatheter mitral valve replacement (TMVR) is a promising new option for treating severe primary mitral regurgitation (MR) in patients at high surgical risk, showing feasibility in early trials with over 100 patients.

TMVR may provide more effective and consistent reduction of MR compared to traditional transcatheter mitral valve repair methods, but further studies with larger patient groups are necessary to establish safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve Replacement: Insights From Early Clinical Experience and Future Challenges. Regueiro, A., Granada, JF., Dagenais, F., 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]

Citations

1. 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 ...

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

2-Year Outcomes of Transcatheter Mitral Valve ... In this study, the impact of TMVR on severity of MR, reduction in HFH rate, and improvement in symptoms was sustained through 2 years.

3. 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) ...

4. jacc.org jacc.org/doi/10.1016/j.jacc.2021.08.060

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 ...

5. 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 ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.068847

Contemporary Outcomes and Trends for the Transseptal ... The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in- ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)02073-2/fulltext?rss=yes

Percutaneous transcatheter valve replacement in ... Percutaneous transseptal TMVR with the SAPIEN M3 system effectively reduced mitral regurgitation with low rates of complications and mortality.

8. cedars-sinai.org cedars-sinai.org/newsroom/study-transcatheter-mitral-valve-repair-safe-successful/

Study: Transcatheter Mitral Valve Repair Safe, Successful Mitral regurgitation success was shown in 88.9% of patients. At 30 days, the incidence of death was 2.7%, stroke was 1.2% and mitral valve ...