Percutaneous vs Surgical Repair for Mitral Valve Regurgitation

(PRIMARY Trial)

Recruiting at45 trial locations

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Annetine Gelijns

Must not be taking: Investigational drugs

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a prospective, multicenter, open-label, randomized trial comparing mitral valve (MV) transcatheter edge-to-edge repair (TEER) to surgical repair (1:1 ratio) in patients with primary, degenerative mitral regurgitation (MR). The trial will be conducted in the U.S., Canada, Germany and the United Kingdom, and is designed as a strategy trial. Thus, all devices legally marketed for TEER of primary degenerative MR in a particular country are eligible to be used in this trial.

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 data supports the effectiveness of this treatment for mitral valve regurgitation?

Research shows that transcatheter edge-to-edge repair (TEER) is an effective treatment for mitral valve regurgitation, providing symptom relief and improved outcomes, especially for patients who are not suitable for open heart surgery. ^{1 2 3 4 5}

Is transcatheter edge-to-edge repair (TEER) for mitral valve regurgitation safe?

TEER, including the MitraClip system, is generally considered safe for treating mitral valve regurgitation, with studies showing it as a less invasive option for patients. However, there may be a need for further surgical intervention in some cases, and safety data is still being gathered. ^{1 3 4 6 7}

How is the Mitral valve TEER treatment different from other treatments for mitral valve regurgitation?

Mitral valve TEER (Transcatheter Edge-to-Edge Repair) is unique because it is a less invasive procedure compared to traditional open-heart surgery, making it suitable for patients who are at high risk for surgical complications. It involves using a device like the MitraClip to repair the valve through a catheter, which is inserted through a small incision, reducing recovery time and hospital stay. ^{1 3 4 6 8}

Research Team

Martin Leon, MD

Principal Investigator

Columbia University

Patrick O'Gara, MD

Principal Investigator

Brigham and Women's Hospital

Joann Chikwe, MD

Principal Investigator

Cedars Sinai

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Mitral valve repair (Procedure)
• TEER (Device)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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 1,022 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]

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 1,044 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]

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]

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]

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]

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]

References

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

Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study. [2023]

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

Outcomes Stratified by Adapted Inclusion Criteria After Mitral Edge-to-Edge Repair. [2022]

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

Short-Term Outcomes Following Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry. [2023]

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

Outcomes After Transcatheter Edge-to-Edge Mitral Valve Repair According to Mitral Regurgitation Etiology and Cardiac Remodeling. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Surgical Removal of a Detached Mitral Valve Repair Clip to Resolve Cardiogenic Shock. [2022]

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

Mitral Surgery After Transcatheter Edge-to-Edge Repair: Society of Thoracic Surgeons Database Analysis. [2022]

7. Poland pubmed.ncbi.nlm.nih.gov

Transcatheter edge-to-edge mitral valve repair in patients with acute decompensated heart failure due to severe mitral regurgitation. [2023]

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

Mitral valve surgery after failed MitraClip-Operation for the inoperable? [2023]