SAPIEN M3 System for Mitral Valve Regurgitation

(ENCIRCLE Trial)

Recruiting at 58 trial locations

Overseen By Edwards THV Clinical Affairs

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Edwards Lifesciences

Must not be taking: Oral steroids, Antibiotics

Disqualifiers: Severe pulmonary hypertension, Renal insufficiency, Liver 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: 1

Duration: Procedure day

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and effectiveness of a new treatment for individuals with moderate to severe mitral valve regurgitation, a condition where the heart's mitral valve doesn't close properly, causing blood to flow backward. The treatment, known as the SAPIEN M3 System (a transcatheter mitral valve replacement system), targets those unable to undergo traditional surgery or other available treatments. The trial includes different groups: one for those who can't receive standard treatments, another for individuals with calcium build-up in the heart, and a third for those whose previous valve repair attempts were unsuccessful. Individuals with noticeable mitral valve issues for whom current treatments aren't viable might be suitable candidates for this trial.

As an unphased trial, this study provides a unique opportunity to explore a new treatment option that might not be available elsewhere.

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 prior data suggests that the SAPIEN M3 System is safe for treating mitral valve regurgitation?

Research has shown that the SAPIEN M3 system, a treatment for mitral valve regurgitation (when the heart's mitral valve doesn't close properly), is generally safe for patients. Studies indicate that it effectively reduces this condition while maintaining low complication and death rates. Most patients did not experience major problems after the procedure.

One study found that patients using SAPIEN M3 had a high success rate in eliminating mitral regurgitation, which is a positive outcome. Another source noted that this system works well even for high-risk patients, suggesting it is well-tolerated. While every treatment carries risks, the available data on SAPIEN M3 shows promising safety results. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the SAPIEN M3 System for mitral valve regurgitation because it offers a pioneering approach to treating patients who aren't suitable for traditional surgical or transcatheter options. Unlike the standard surgical and percutaneous procedures, this system allows for a transcatheter mitral valve replacement (TMVR), which is less invasive and potentially safer for high-risk patients. The SAPIEN M3 System is designed to accommodate challenging cases, like those with mitral annular calcification or failed previous repairs, providing a much-needed alternative where existing treatments fall short. This flexibility and adaptability make it a promising option for patients with limited choices.

What evidence suggests that the SAPIEN M3 System is effective for mitral valve regurgitation?

Research has shown that the SAPIEN M3 System effectively treats mitral valve regurgitation (MR). In this trial, participants will receive the SAPIEN M3 System through transcatheter mitral valve replacement (TMVR). One study found that 95.7% of patients who received this treatment experienced little to no MR after the procedure. The system reduces MR with a low risk of complications or death. It is designed to fit well in the heart without blocking blood flow, making it a suitable option for patients unable to undergo traditional surgery. ^{1 2 3 4 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• SAPIEN M3 System

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.

How Is the Trial Designed?

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.

SAPIEN M3 System is already approved in European Union, United States for the following indications:

Approved in European Union as SAPIEN M3 System for:

• Symptomatic, at least 3+ mitral regurgitation (MR)

Approved in United States as SAPIEN M3 System for:

• Not yet approved; expected approval by the end of 2025 for symptomatic, at least 3+ mitral regurgitation (MR)

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. 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.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1553838925003471

The SAPIEN M3 system for transcatheter mitral valve ... The SAPIEN M3 system enables fully percutaneous TMVR in high-risk patients with mitral regurgitation. A self-expanding nitinol dock provides anatomy- ...

3. edwards.com edwards.com/newsroom/news/2025-10-27-successful-patient-outcomes-demonstrated-with-edwa

Press releases Further, patients receiving the SAPIEN M3 valve therapy achieved substantial mitral regurgitation (MR) elimination (95.7% MR ≤ 0/1+) and ...

4. scai.org scai.org/encircle-1-year-outcomes-transcatheter-mitral-valve-replacement-tmvr-sapien-m3-system-patients

ENCIRCLE: 1-Year Outcomes of Transcatheter Mitral Valve ... The one-year data of transcatheter mitral valve replacement (TMVR) outcomes from the ENCIRCLE trial represent a meaningful step forward in ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40610339/

The SAPIEN M3 system for transcatheter mitral valve ... This design minimizes the risk of left ventricular outflow tract (LVOT) obstruction and enables stable, anatomy-independent anchoring without ...

6. tctmd.com tctmd.com/news/encircle-good-results-sapien-m3-transseptal-tmvr

ENCIRCLE: Good Results With Sapien M3 Transseptal ... The mean STS predicted risk of 30-day mortality for mitral valve replacement was 6.6%, with 28.8% of patients being considered high risk with a ...