Percutaneous vs Surgical Repair for Mitral Valve Regurgitation

(PRIMARY Trial)

Recruiting at 70 trial locations

Overseen By Ellen Moquete, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Annetine Gelijns

Must not be taking: Investigational drugs

Disqualifiers: Non-degenerative MR, Cardiomyopathy, CAD, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 month

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to fix a leaky mitral valve. One method involves surgery, while the other uses a less invasive technique with a tiny device to repair the valve without open-heart surgery, known as Transcatheter Edge-to-Edge Repair (TEER). Researchers aim to determine which treatment works best for individuals with serious mitral valve issues who can undergo either procedure. It suits adults advised to have their mitral valve repaired and eligible for both methods. As an unphased trial, this study allows patients to contribute to important research that could enhance treatment options for mitral valve repair.

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 healthcare provider.

What prior data suggests that these mitral valve repair techniques are safe?

Research has shown that surgical mitral valve repair is very safe. For most patients with primary mitral regurgitation, the risk of dying from the surgery is very low, around 0.83%, meaning over 99% of patients survive the procedure. The surgery also proves successful in the long term, often lasting as long as a valve replacement, and sometimes even better.

Transcatheter edge-to-edge repair (TEER) has also been proven safe and effective. Studies indicate that about 86% of patients have the device placed successfully, and nearly 90% experience improvement in their condition. Although the risk of death within 30 days is higher than with surgery, TEER still shows promise in reducing future hospital visits due to heart failure.

Both options have distinct safety profiles, but overall, they are considered safe and well-tolerated for treating mitral valve issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments for mitral valve regurgitation because they offer less invasive options compared to traditional open-heart surgery. The transcatheter edge-to-edge repair (TEER) is performed using a catheter, allowing for quicker recovery times and reduced surgical risks. This method provides a promising alternative for patients who may not be suitable candidates for surgery, expanding access to treatment. On the other hand, surgical mitral valve repair remains a robust option, offering a more direct approach to fixing the valve, which may be necessary for certain patients. Together, these options could lead to personalized treatment plans, improving outcomes for those with this heart condition.

What evidence suggests that this trial's treatments could be effective for mitral valve regurgitation?

This trial will compare surgical mitral valve repair with transcatheter edge-to-edge repair (TEER) for treating mitral regurgitation. Research has shown that surgical mitral valve repair is highly effective, with studies indicating that over 99% of patients experience little to no mitral regurgitation after surgery and face a low risk of complications like blood clots and valve infections. For those in the TEER arm, research has also shown its effectiveness, with over 90% of patients experiencing a significant reduction in mitral regurgitation severity within a year. TEER boasts a high success rate of 98.4%, indicating the procedure is almost always performed successfully. Both treatments are safe and help reduce the need for future hospital visits and complications. ^{4 6 7 8 9}

Who Is on the Research Team?

Joanna Chikwe, MD

Principal Investigator

Cedars Sinai

Martin Leon, MD

Principal Investigator

Columbia University

Patrick O'Gara, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 65 or older with a specific heart valve condition called primary degenerative mitral regurgitation. Candidates must be able to perform physical tests and complete health questionnaires, and are eligible across all surgical risk levels. Exclusions include recent febrile illness, need for other heart surgeries, certain allergic reactions, bleeding disorders, prior mitral interventions, and severe co-existing conditions.

Inclusion Criteria

If you have atrial fibrillation and need both catheter-based and surgical ablation, your local heart team must confirm that you are eligible for both procedures.

I am 65 or older with severe valve leakage as shown by an echo test.

My heart condition is considered low, intermediate, or high risk by my medical team.

Exclusion Criteria

You might not be able to keep up with the required check-ups and appointments.

I have a thickened heart muscle that obstructs blood flow.

You have secondary or functional mitral regurgitation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either mitral valve transcatheter edge-to-edge repair (TEER) or surgical repair

1 month

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual visits (in-person)

Long-term follow-up

Participants are followed for up to 10 years post intervention for particular endpoints

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Mitral valve repair
• TEER

Trial Overview The PRIMARY trial compares two treatments for mitral valve prolapse: a less invasive procedure called transcatheter edge-to-edge repair (TEER) versus traditional surgery. Participants will be randomly assigned to one of the two options in equal numbers at multiple centers internationally.

How Is the Trial Designed?

Group I: Surgical mitral valve repair Active Control 1 Intervention

Patients who are randomized to the surgical arm will undergo mitral surgery.

Group II: Transcatheter edge-to-edge repair Active Control 1 Intervention

In the transcatheter edge-to-edge repair arm, patients will be treated with a commercially-approved edge-to-edge mitral repair device.

Mitral valve repair is already approved in United States, European Union, Canada for the following indications:

Approved in United States as MitraClip for:

• Primary degenerative mitral regurgitation
• Secondary mitral regurgitation in heart failure patients

Approved in European Union as MitraClip for:

• Primary degenerative mitral regurgitation
• Secondary mitral regurgitation in heart failure patients

Approved in Canada as MitraClip for:

• Primary degenerative mitral regurgitation
• Secondary mitral regurgitation in heart failure patients

Who Is Running the Clinical Trial?

Annetine Gelijns

Lead Sponsor

Trials

3

Recruited

870+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 124 patients with significant mitral regurgitation, the PASCAL transcatheter valve repair system showed a 75% survival rate and a 73% rate of freedom from heart failure hospitalization after 3 years, indicating its long-term efficacy.

The procedure successfully reduced mitral regurgitation to levels of 2+ or less in 93% of patients and improved heart function, with 89% achieving NYHA class I/II status, demonstrating both safety and effectiveness in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study. Spargias, K., Lim, DS., Makkar, R., et al.[2023]

In a study of 1,044 patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR), those with functional MR (a-FMR and v-FMR) experienced worse clinical outcomes compared to those with degenerative MR (DMR) over a 2-year period.

Despite similar rates of residual MR after the procedure, patients with a-FMR and v-FMR had significantly higher rates of all-cause mortality and heart failure hospitalization (31.5% and 42.3%, respectively) compared to 21.6% in the DMR group, indicating that the etiology of MR impacts long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes After Transcatheter Edge-to-Edge Mitral Valve Repair According to Mitral Regurgitation Etiology and Cardiac Remodeling. Yoon, SH., Makar, M., Kar, S., et al.[2022]

In a study of 463 patients who underwent mitral surgery after transcatheter edge-to-edge repair (TEER), the observed 30-day mortality rate was 10.2%, indicating a higher risk than predicted, especially for urgent surgeries and older patients.

Mitral repair after failed TEER is rare, occurring in only 4.8% of cases, which suggests that careful consideration is needed when choosing TEER as a treatment option, particularly for younger patients with degenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitral Surgery After Transcatheter Edge-to-Edge Repair: Society of Thoracic Surgeons Database Analysis. Chikwe, J., O'Gara, P., Fremes, S., et al.[2022]

In a study of 17 high-risk patients who underwent mitral valve surgery after failed MitraClip procedures, the average 30-day all-cause mortality was 18%, highlighting the significant risks associated with this patient population.

Despite the challenges, the study reported favorable valve-related outcomes post-surgery, with only a 6% rate of valve-related mortality and a low incidence of severe paravalvular leaks, indicating that careful patient evaluation is crucial for managing complications after MitraClip failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitral valve surgery after failed MitraClip-Operation for the inoperable? Gerfer, S., Ivanov, B., Großmann, C., et al.[2023]

The OCEAN-Mitral Registry included 2,150 patients with mitral regurgitation, showing a high acute procedural success rate of 94.6% for both the second-generation (G2) and fourth-generation (G4) MitraClip systems, indicating the efficacy of transcatheter edge-to-edge repair (TEER).

The use of the G4 system resulted in shorter device and fluoroscopy times compared to the G2 system, suggesting potential improvements in procedural efficiency as experience with the G4 system increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes Following Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry. Saji, M., Yamamoto, M., Kubo, S., et al.[2023]

In a study of 1,022 patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER), applying adapted COAPT enrollment criteria identified a group with significantly lower mortality rates compared to those who did not meet these criteria (P < 0.001).

Stratifying patients based on adapted MITRA-FR criteria showed no significant difference in all-cause mortality (P = 0.19), indicating that the COAPT criteria may better predict outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes Stratified by Adapted Inclusion Criteria After Mitral Edge-to-Edge Repair. Koell, B., Orban, M., Weimann, J., et al.[2022]

Transcatheter edge-to-edge mitral valve repair (TEER) can effectively relieve symptoms in patients who are not candidates for open heart surgery, but there are risks associated with the procedure, such as clip embolization leading to ventricular arrhythmias.

In this case, a patient experienced serious complications from clip embolization after TEER, necessitating an emergency surgical intervention to remove the clip and replace the mitral valve, highlighting the importance of monitoring for potential complications post-procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Removal of a Detached Mitral Valve Repair Clip to Resolve Cardiogenic Shock. Wedin, JO., Karlsson, P., Holm, L., et al.[2022]

Transcatheter edge-to-edge mitral valve repair (TEER) is a safe and effective treatment for hospitalized patients with acute decompensated heart failure and severe mitral regurgitation, achieving a 97% procedural success rate and significant reduction in MR severity in 74% of cases.

Although there is a high early mortality rate of 23% at 30 days, patients who survive beyond 6 months experience good long-term outcomes, with all survivors having mild or no mitral regurgitation and being free of heart failure hospitalizations at 1 year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter edge-to-edge mitral valve repair in patients with acute decompensated heart failure due to severe mitral regurgitation. Makmal, N., Silbermintz, N., Faierstein, K., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7940942/

Clinical outcomes following surgical mitral valve repair or ... Mitral valve repair (MVP) has a lower rate of reoperation, thromboembolism, and valve infection compared to mitral valve replacement (MVR).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38346705/

Early and Late Results after Surgical Mitral Valve Repair Freedom from more than moderate MR was > 99%. Thirty-day mortality was 0.2% and did not differ significantly between groups (p = 0.37). Median ...

3. 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 ...

4. jacc.org jacc.org/doi/10.1016/j.jacc.2023.01.001

Benchmarking Mitral Valve Repair: Defining Standards for ... This real-world analysis found that mortality after mitral valve repair was uncommon, and only marginally influenced by surgical volume and experience.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666273624002353

Mitral valve replacement versus repair for severe ... This study compares early and long-term outcomes following mitral valve (MV) repair and replacement in patients with mitral regurgitation (MR) and reduced ...

6. jacc.org jacc.org/doi/10.1016/j.jacc.2022.11.017

Risk of Surgical Mitral Valve Repair for Primary ... - JACC Finally, the expected mortality in two-thirds of all primary MR patients was <1%, with the 90th percentile OM being only 2.5%. These data help ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4356723/

Long-term Outcomes of Mitral Valve Repair Versus ... In the publications in this review, mitral valve repair was found to have long-term durability equaling that of replacement, and in some contexts, better.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0735109722074186

Risk of Surgical Mitral Valve Repair for Primary ... In primary mitral regurgitation, operative mortality is very low for isolated mitral valve (MV) repair without concomitant procedures: mean 0.83%, median 0.43%, ...

9. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.123.013782

One-Year Outcomes of Transseptal Mitral Valve-in- ... Similarly, 30-day mortality after MViV has improved from 8.2% in early experience, to 6.5% in the Valve-in-Valve International Data (VIVID) ...