SAPIEN M3 System for Mitral Valve Regurgitation

(ENCIRCLE Trial)

Recruiting at55 trial locations

Overseen by Mayra Guerrero, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Edwards Lifesciences

Must not be taking: Oral steroids, Antibiotics

Disqualifiers: Severe pulmonary hypertension, Renal insufficiency, Liver disease, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial will test the safety and effectiveness of the SAPIEN M3 System in patients with severe mitral regurgitation who can't use other treatments. The device helps the heart valve close properly to stop it from leaking. The SAPIEN transcatheter heart valve (THV) has been previously tested and shown to be safe and effective in the pulmonary position.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, your heart failure management must be stable for at least 30 days before joining the trial.

What data supports the effectiveness of the SAPIEN M3 System treatment for Mitral Valve Regurgitation?

The SAPIEN 3 valve, a component of the SAPIEN M3 System, has shown high technical success and sustained valve performance in treating failed surgical mitral bioprostheses and mitral valve disease in both adults and children. However, outcomes can vary, and complications may occur, highlighting the need for careful planning and experienced operators. ^{1 2 3 4 5}

Is the SAPIEN M3 System safe for humans?

The SAPIEN 3 valve, a related device, has been shown to be safe in humans for treating aortic stenosis, with improvements in reducing leaks and good clinical outcomes. ^{6 7 8 9 10}

What makes the SAPIEN M3 System treatment unique for mitral valve regurgitation?

The SAPIEN M3 System is unique because it is a transcatheter mitral valve replacement option that can be used in patients with previous mitral surgical rings or mitral annular calcification, where traditional surgery might be too risky. It uses a minimally invasive approach, which can be safer for high-risk patients compared to open-heart surgery. ^{1 2 5 7 11}

Research Team

John Webb, MD

Principal Investigator

St. Paul's Hospital

Mayra Guerrero, MD

Principal Investigator

Mayo Clinic

David Daniels, MD

Principal Investigator

California Pacific Medical Center

Eligibility Criteria

The ENCIRCLE Trial is for adults with severe mitral valve regurgitation who can't have standard surgery or other transcatheter treatments. They must be stable after heart failure management and not pregnant, in another trial, or have conditions like recent heart attacks, untreated coronary disease, certain anatomy issues, severe lung problems, or life expectancy under a year.

Inclusion Criteria

My heart condition cannot be treated with standard surgery or catheter procedures.

My heart failure treatment has been stable for at least 30 days.

I am 18 years old or older.

Exclusion Criteria

I am currently pregnant or breastfeeding.

I cannot take blood thinning medications due to a health condition.

I have severe, untreatable high blood pressure in my lungs.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo transcatheter mitral valve replacement (TMVR) using the SAPIEN M3 System

Procedure day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TMVR, including assessment of LVEDVi, NYHA class, KCCQ score, and MR improvement

1 year

Regular follow-up visits (in-person)

Continued Access

Eligible participants may enroll in the continued access phase of the trial

Treatment Details

Interventions

• SAPIEN M3 System (Heart Valve Replacement)

Trial Overview This study tests the SAPIEN M3 System's safety and effectiveness for patients with symptomatic mitral regurgitation deemed unsuitable for other treatments. Participants will receive the SAPIEN M3 valve and dock to correct their condition.

Participant Groups

Group I: TMVR - Main Cohort Experimental Treatment 1 Intervention

Subjects for whom commercially available surgical or transcatheter treatment options are deemed unsuitable will have transcatheter mitral valve replacement (TMVR).

Group II: TMVR - MAC Registry Experimental Treatment 1 Intervention

Subjects with mitral annular calcification (MAC) will have TMVR.

Group III: TMVR - Failed TEER Registry Experimental Treatment 1 Intervention

Subjects who have had an attempted but failed transcatheter edge-to-edge repair (TEER) procedure will have TMVR.

Who Is Running the Clinical Trial?

Edwards Lifesciences

Lead Sponsor

Trials

188

Recruited

67,500+

Founded

1958

Headquarters

Irvine, California, U.S.

Known For

Structural Heart Innovations

Top Products

SAPIEN Transcatheter Heart Valve, EVOQUE System, PASCAL Precision, SAPIEN M3

Todd Brinton

Edwards Lifesciences

Chief Medical Officer since 2023

MD from Stanford University

Bernard Zovighian

Edwards Lifesciences

Chief Executive Officer since 2023

MBA from INSEAD

Findings from Research

The SAPIEN 3 transcatheter heart valve is currently the only option for patients needing mitral valve replacement in cases of previous surgical rings or calcification, but outcomes have been inconsistent.

To improve results with the SAPIEN 3 valve, the authors recommend a comprehensive approach that includes modifications to the valve and delivery system, as well as careful planning and management by experienced medical teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Art of SAPIEN 3 Transcatheter Mitral Valve Replacement in Valve-in-Ring and Valve-in-Mitral-Annular-Calcification Procedures. Babaliaros, VC., Lederman, RJ., Gleason, PT., et al.[2022]

Transcatheter mitral valve-in-valve (TMVIV) using the Sapien 3 valve has a high technical success rate, but complications can occur, as demonstrated in a case where the valve embolized twice during the procedure.

The case highlights a successful technique for repositioning a dislodged valve by using the delivery sheath as a pusher, which allowed for the safe deployment of the valve after initial complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A valve embolized twice: a case report of Sapien 3 embolization in left ventricle and left atrium during transcatheter transapical mitral valve-in-valve implantations for a failed bioprosthesis. Lin, HC., Lee, YT., Tsao, TP., et al.[2023]

Transcatheter mitral valve-in-valve implantation in four pediatric patients with dysfunctional bioprosthetic mitral valves showed significant improvement, with the mean transmitral gradient dropping from 19.75 mm Hg to 1 mm Hg after the procedure.

The procedure was performed safely, with patients experiencing improved functional class from NYHA class IV to class I, suggesting it is a viable alternative for high-risk patients who cannot undergo traditional surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve-in-Valve Implantation in Pediatric Patients. Al Nasef, M., Alsahari, A., Eltayeb, A., et al.[2022]

The surgical implantation of the Edwards Sapien 3 valve in a severely ill child with prosthetic valve endocarditis was performed safely, demonstrating effective short-term hemodynamic results.

This case suggests that the Sapien 3 valve is a promising option for treating mitral valve disease in children, particularly when a bioprosthesis is needed during valve re-replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edwards Sapien 3 Valve for Mitral Replacement in a Child After Melody Valve Endocarditis. Trezzi, M., Cetrano, E., Iacobelli, R., et al.[2017]

In the MITRAL trial, 30 high-risk patients with failed surgical mitral bioprostheses underwent transseptal mitral valve-in-valve (MViV) using the SAPIEN 3 valve, achieving a 100% technical success rate and low 30-day mortality of 3.3%.

At 1-year follow-up, 82.8% of patients maintained effective valve performance with no significant mitral regurgitation, and 89.3% reported improved symptoms, indicating that this procedure is both safe and effective for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. Guerrero, M., Pursnani, A., Narang, A., et al.[2022]

The Edwards SAPIEN transcatheter heart valve (THV) is considered noninferior to traditional surgical aortic valve replacement for high-risk operable patients, based on the high-risk arm of the PARTNER trial.

Despite some concerns about safety and trial misconduct, the FDA panel unanimously agreed that the benefits of the Edwards SAPIEN THV outweigh the risks, leading to its approval for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the 2012 Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee meeting on the Edwards SAPIEN transcatheter heart valve for high-risk aortic stenosis patients. Barbash, IM., Dvir, D., Waksman, R.[2013]

The SAPIEN 3 transcatheter valve demonstrated high safety and efficacy, with 96.4% of patients experiencing none to mild paravalvular regurgitation and a low mortality rate of 2.1% when using the transfemoral approach.

This third-generation valve shows promise as a viable alternative to high- or intermediate-risk surgical options for severe aortic stenosis, particularly due to its improved ease of use and accuracy in positioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter evaluation of a next-generation balloon-expandable transcatheter aortic valve. Webb, J., Gerosa, G., Lefèvre, T., et al.[2022]

Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe aortic stenosis who are at moderate to high surgical risk, demonstrating significant efficacy in clinical trials.

Newer-generation devices, such as the SAPIEN-3 and CENTERA valves, have shown improvements in reducing paravalvular leaks and achieving excellent clinical outcomes, indicating advancements in TAVI technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer-generation of Edwards transcatheter aortic valve systems: SAPIEN 3, Centera, and SAPIEN 3 Ultra. Solomonica, A., Choudhury, T., Bagur, R.[2019]

In a study of 235 patients with severe aortic stenosis, the use of the Edwards Sapien 3 valve for transcatheter aortic valve implantation (TAVI) resulted in no cases of moderate or severe residual aortic regurgitation, indicating high device success.

The procedure, performed without general anesthesia, showed low rates of major vascular complications (3.0%), mortality (2.6%), and stroke (2.1%) within 30 days, demonstrating its safety and efficacy across different valve sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience. Wöhrle, J., Gonska, B., Rodewald, C., et al.[2019]

The LOTUS valve system and the Edwards SAPIEN 3 prosthesis showed comparable early safety outcomes in treating aortic stenosis, with similar rates of complications (14.3% for LOTUS vs. 14.6% for Edwards SAPIEN 3).

However, patients receiving the LOTUS valve had a significantly higher rate of requiring a permanent pacemaker (34.3% for LOTUS vs. 14.1% for Edwards SAPIEN 3), indicating a potential drawback in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repositionable Versus Balloon-Expandable Devices for Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis. Pilgrim, T., Stortecky, S., Nietlispach, F., et al.[2018]

An 86-year-old patient with high surgical risks successfully received a transcatheter mitral valve implant using the Sapien 3 valve within a failed bioprosthetic valve, demonstrating a new treatment option for high-risk patients.

Post-procedure echocardiograms showed satisfactory results, and the patient was discharged without complications, indicating the safety and efficacy of this innovative approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transapical Transcatheter Mitral Valve-in-Valve Implantation Using an Edwards SAPIEN 3 Valve. He, C., Scalia, G., Walters, DL., et al.[2022]

References

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

The Art of SAPIEN 3 Transcatheter Mitral Valve Replacement in Valve-in-Ring and Valve-in-Mitral-Annular-Calcification Procedures. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A valve embolized twice: a case report of Sapien 3 embolization in left ventricle and left atrium during transcatheter transapical mitral valve-in-valve implantations for a failed bioprosthesis. [2023]

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

Transcatheter Mitral Valve-in-Valve Implantation in Pediatric Patients. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Edwards Sapien 3 Valve for Mitral Replacement in a Child After Melody Valve Endocarditis. [2017]

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

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. [2022]

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

Overview of the 2012 Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee meeting on the Edwards SAPIEN transcatheter heart valve for high-risk aortic stenosis patients. [2013]

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

Multicenter evaluation of a next-generation balloon-expandable transcatheter aortic valve. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Newer-generation of Edwards transcatheter aortic valve systems: SAPIEN 3, Centera, and SAPIEN 3 Ultra. [2019]

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

Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Repositionable Versus Balloon-Expandable Devices for Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis. [2018]

11. Australia pubmed.ncbi.nlm.nih.gov

Transapical Transcatheter Mitral Valve-in-Valve Implantation Using an Edwards SAPIEN 3 Valve. [2022]