Siegel TAVR for Aortic Stenosis

Recruiting at 8 trial locations

Overseen By VP of Regulatory Affairs, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MiRus

Must not be taking: Aspirin, Heparin, Ticlopidine, others

Disqualifiers: Prosthetic heart valve, Severe dementia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post procedure

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a known hypersensitivity or contraindication to certain medications like aspirin, heparin, or clopidogrel, you may need to discuss this with the trial team.

What data supports the effectiveness of the Siegel Transcatheter Aortic Valve (TAVR) treatment for aortic stenosis?

Research shows that TAVR can improve survival and quality of life for patients with severe aortic stenosis, especially those who are at high risk for surgery or cannot undergo surgery at all. ^{1 2 3 4 5}

Is Siegel TAVR generally safe for humans?

Transcatheter aortic valve replacement (TAVR) has been studied extensively and is considered safe for patients with aortic stenosis, especially those at high to intermediate risk. It has also been approved for patients with low surgical risk, indicating its general safety in humans. ^{6 7 8 9 10}

How is the Siegel TAVR treatment for aortic stenosis different from other treatments?

The Siegel TAVR treatment is a less-invasive option for aortic stenosis, using a transcatheter approach to replace the valve without open-heart surgery, which is beneficial for patients at high surgical risk. It may involve unique features like a specific mechanism for valve fixation, similar to the JenaValve's 'clipping-mechanism' that engages the native valve cusps. ^{3 11 12 13 14}

What is the purpose of this trial?

The Siegel™ Transcatheter Aortic Valve (TAVR) early feasibility study objective is to assess the acute and long-term safety and feasibility of the Siegel TAVR device in adult subjects with symptomatic, severe native aortic stenosis eligible for the transcatheter aortic valve replacement.

Eligibility Criteria

This trial is for adults over 50 with severe aortic stenosis who have symptoms and need a valve replacement. They must be suitable for the Siegel TAVR via transfemoral delivery, have an appropriate heart valve size, understand the study, consent to it, and agree to follow-up visits.

Inclusion Criteria

I am a candidate for a heart valve replacement via the leg artery.

My heart valve is right for a specific 26 mm valve replacement.

My heart team has recommended a valve replacement via TAVR.

Exclusion Criteria

I have had a recent heart attack or heart procedure.

I need treatment for a serious heart valve problem.

Pre-existing prosthetic heart valve in any position (except mitral ring)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo the transcatheter aortic valve replacement procedure using the Siegel TAVR device

Immediate post procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of all-cause mortality or disabling stroke

30 days

Long-term follow-up

Participants are monitored for long-term safety and feasibility of the Siegel TAVR device

Long-term

Treatment Details

Interventions

• Siegel Transcatheter Aortic Valve (TAVR)

Trial Overview The Siegel Transcatheter Aortic Valve Replacement System (TAVR) is being tested in people with symptomatic severe native aortic stenosis. The study aims to evaluate its safety and effectiveness both immediately after implantation and in the long term.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

MiRus

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

A systematic review of 20 studies involving 2,775 high surgical-risk patients showed that transcatheter aortic valve replacement (TAVR) significantly improves functional capacity, with an increase of over 40 meters in the 6-minute walk test after the procedure.

Patients also experienced a meaningful enhancement in health-related quality of life (HRQoL), with notable improvements in physical activity scores, indicating that TAVR is a beneficial treatment option for those with severe aortic stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional capacity and health-related quality of life outcomes post transcatheter aortic valve replacement: a systematic review and meta-analysis. Straiton, N., Jin, K., Bhindi, R., et al.[2019]

Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for aortic valve stenosis in patients over 75 years old in Germany, surpassing surgical aortic valve replacement (SAVR) in frequency since 2014.

Despite older patients treated with TAVR having higher operative risks due to age and co-morbidities, the in-hospital mortality rates were relatively low at 3% for transfemoral TAVR, indicating that TAVR can be performed safely in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development and Results of Transcatheter and Surgical Aortic Valve Replacement in Germany 2014 and 2015]. Stachon, P., Kaier, K., Zirlik, A., et al.[2019]

In a study of 72,356 hospitalizations for aortic valve replacement in patients under 60, TAVR showed lower procedural complications compared to SAVR, while maintaining a similar mortality rate (2.9% vs. 3.0%).

TAVR patients experienced a shorter hospital stay (4 days vs. 6 days) without a significant difference in 30-day readmission rates, indicating favorable short-term outcomes for younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients Gad, MM., Elgendy, IY., Saad, AM., et al.[2022]

In a study of 2137 patients undergoing transcatheter aortic valve replacement (TAVR), a significant 33% experienced poor outcomes within 6 months, defined by death or a decline in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire.

Predictive models were developed to identify patients at high risk for poor outcomes after TAVR, successfully identifying 10% of patients with a greater than 50% likelihood of poor outcomes at 6 months and 52% at 1 year, which can help inform treatment decisions and set realistic expectations for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (Placement of Aortic Transcatheter Valve) trial. Arnold, SV., Reynolds, MR., Lei, Y., et al.[2022]

Transcatheter aortic valve replacement (TAVR) significantly improves life expectancy and quality of life for patients with severe aortic stenosis who cannot undergo surgery, increasing life expectancy from 2.08 to 2.93 years and quality-adjusted life expectancy from 1.19 to 1.93 years.

While TAVR reduces hospitalizations, it also increases the risk of complications like stroke and raises lifetime costs, making it a more expensive option compared to medical management, with an incremental cost-effectiveness of $116,500 per quality-adjusted life-year gained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve replacement in nonsurgical candidates with severe, symptomatic aortic stenosis: a cost-effectiveness analysis. Simons, CT., Cipriano, LE., Shah, RU., et al.[2013]

The LRT study is the first FDA-approved trial investigating the safety and effectiveness of transcatheter aortic valve replacement (TAVR) in low-risk patients with symptomatic severe aortic stenosis, aiming to establish its feasibility compared to traditional surgical methods.

Patients will be monitored for 5 years post-procedure, with assessments for complications like subclinical leaflet thrombosis and regular echocardiograms to ensure the proper functioning of the valve, providing a comprehensive evaluation of TAVR's long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of transcatheter aortic valve replacement in low-risk patients with symptomatic severe aortic stenosis: Rationale and design of the Low Risk TAVR (LRT) study. Rogers, T., Torguson, R., Bastian, R., et al.[2017]

Transfemoral aortic valve replacement (TAVR) shows lower 30-day mortality rates compared to surgical aortic valve repair (SAVR), indicating a safety advantage in the early postoperative period.

However, TAVR is associated with higher rates of moderate-severe paravalvular leak and pacemaker implantation, suggesting that while it may reduce early mortality, it also presents specific risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical vs transfemoral aortic valve replacement in low-risk patients: An updated meta-analysis of trial and registry data. Luthra, S., Leiva-Juárez, MM., Ohri, SK.[2021]

Transcatheter aortic valve replacement (TAVR) is a safe and effective treatment for patients with symptomatic aortic stenosis who are at very high risk for traditional surgery, with a 30-day hospital mortality rate of 8%, similar to outcomes from the PARTNER trials.

In a study of 160 patients evaluated for TAVR, 31% were deemed appropriate candidates, and the implementation of lessons from previous trials allowed for a short learning curve and successful outcomes in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve replacement program in the post-food and drug administration approval era: early outcomes at an academic medical center. Melby, SJ., Bess, KM., Isbell, KD., et al.[2015]

About 9.5% of patients receiving transcatheter aortic valve replacement (TAVR) in the U.S. were treated for off-label indications, which include conditions like bicuspid valve and severe mitral regurgitation.

Patients receiving off-label TAVR had higher in-hospital and 30-day mortality rates compared to those receiving on-label TAVR, but after one year, mortality rates were similar, indicating a need for further research on the safety and efficacy of off-label TAVR use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends and Outcomes of Off-label Use of Transcatheter Aortic Valve Replacement: Insights From the NCDR STS/ACC TVT Registry. Hira, RS., Vemulapalli, S., Li, Z., et al.[2020]

In lower risk patients, transcatheter aortic valve replacement (TAVR) shows a lower risk of 30-day mortality, stroke, bleeding complications, and acute kidney injury compared to surgical aortic valve replacement (SAVR), suggesting it may be a safer option.

However, TAVR is associated with a higher risk of vascular complications, moderate or severe paravalvular leak, and the need for permanent pacemaker implantation, indicating that while TAVR is effective, it also carries specific risks that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Lower Surgical Risk Scores: A Systematic Review and Meta-Analysis of Early Outcomes. Arora, S., Strassle, PD., Ramm, CJ., et al.[2020]

The JenaValve transcatheter heart valve (THV) demonstrated a high procedural success rate of 95% in a study of 180 high-risk patients with aortic stenosis, indicating its safety and effectiveness for transapical aortic valve replacement (TA-TAVR).

At one-year follow-up, the JenaValve showed a combined efficacy of 80.8% and no significant complications such as annular rupture or coronary ostia obstruction, suggesting it is a reliable option for patients with specific anatomical challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The JUPITER registry: 1-year results of transapical aortic valve implantation using a second-generation transcatheter heart valve in patients with aortic stenosis. Silaschi, M., Treede, H., Rastan, AJ., et al.[2017]

In a study of 226 patients with prior coronary artery bypass graft surgery, transcatheter aortic valve replacement (TAVR) showed a lower all-cause mortality rate at 1 year (9.6%) compared to surgical aortic valve replacement (SAVR) (18.1%), suggesting a potential survival advantage for TAVR.

TAVR also demonstrated a significant reduction in complications such as longer hospital stays, acute kidney injury, and major adverse events compared to SAVR, indicating a better overall safety profile for patients undergoing TAVR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter or Surgical Aortic Valve Replacement in Patients With Prior Coronary Artery Bypass Grafting. Conte, JV., Gleason, TG., Resar, JR., et al.[2022]

In a study involving 200 low-risk patients undergoing TAVR for severe aortic stenosis, there was zero all-cause mortality and zero in-hospital strokes at 30 days, indicating high safety and efficacy of the procedure in this population.

TAVR demonstrated low rates of complications, with only 3.0% experiencing new-onset atrial fibrillation and a short average hospital stay of 2 days, although 14% showed signs of subclinical leaflet thrombosis at 30 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Aortic Stenosis. Waksman, R., Rogers, T., Torguson, R., et al.[2022]

Transcatheter aortic valve replacement (TAVR) is an effective and less-invasive treatment for high-risk patients with severe aortic stenosis, but it comes with complications such as strokes and vascular events that need to be addressed through improved procedures and technology.

Future advancements in TAVR, including new systems and accessory devices aimed at reducing complications and expanding treatment indications, hold promise for enhancing patient outcomes and extending the therapy to more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and future opportunities for transcatheter aortic valve therapy. Leon, MB., Gada, H., Fontana, GP.[2019]

References

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

Functional capacity and health-related quality of life outcomes post transcatheter aortic valve replacement: a systematic review and meta-analysis. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

[Development and Results of Transcatheter and Surgical Aortic Valve Replacement in Germany 2014 and 2015]. [2019]

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

Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients [2022]

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

Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (Placement of Aortic Transcatheter Valve) trial. [2022]

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

Transcatheter aortic valve replacement in nonsurgical candidates with severe, symptomatic aortic stenosis: a cost-effectiveness analysis. [2013]

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

Feasibility of transcatheter aortic valve replacement in low-risk patients with symptomatic severe aortic stenosis: Rationale and design of the Low Risk TAVR (LRT) study. [2017]

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

Surgical vs transfemoral aortic valve replacement in low-risk patients: An updated meta-analysis of trial and registry data. [2021]

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

Transcatheter aortic valve replacement program in the post-food and drug administration approval era: early outcomes at an academic medical center. [2015]

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

Trends and Outcomes of Off-label Use of Transcatheter Aortic Valve Replacement: Insights From the NCDR STS/ACC TVT Registry. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Lower Surgical Risk Scores: A Systematic Review and Meta-Analysis of Early Outcomes. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

The JUPITER registry: 1-year results of transapical aortic valve implantation using a second-generation transcatheter heart valve in patients with aortic stenosis. [2017]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Transcatheter or Surgical Aortic Valve Replacement in Patients With Prior Coronary Artery Bypass Grafting. [2022]

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

Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Aortic Stenosis. [2022]

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

Challenges and future opportunities for transcatheter aortic valve therapy. [2019]