Transcatheter Edge-to-Edge Repair for Mitral Valve Regurgitation

(MINOS Trial)

Recruiting at 3 trial locations

Overseen By Pietro Di Santo, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Disqualifiers: Coronary revascularization, Degenerative MR, Thrombus, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

Mitral regurgitation may be seen in the setting of cardiogenic shock. Transcatheter edge-to-edge repair (TEER) has been shown to improve outcomes in patients with chronic heart failure. Observational studies suggest improvements in clinical outcomes in patients with mitral regurgitation in the setting of cardiogenic shock; however, there remains a lack of randomized clinical data to support the use of TEER in cardiogenic shock. This study will be a multicenter, open-label, randomized-controlled trial with two study arms: medical therapy and TEER. Patients admitted to the Cardiac Intensive Care Unit (CICU), Cardiac Surgery Intensive Care Unit (CSICU) or Intensive Care Units (ICU) at participating centers will be recruited. The study aims to answer the question: "Does TEER in patients with SCAI stage C or D cardiogenic with concomitant moderate or greater mitral regurgitation improve outcomes as compared to medical therapy?" The study hypothesis is that TEER will lead to an overall improvement in the composite outcome as compared to the medical therapy arm.

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 study team to get a clear answer.

What data supports the effectiveness of the treatment Transcatheter Edge-to-Edge Repair (TEER) for Mitral Valve Regurgitation?

Research shows that TEER with MitraClip improves outcomes for patients with moderate-to-severe and severe mitral regurgitation, making it a promising less invasive option for those who are not ideal candidates for surgery. ^{1 2 3 4 5}

Is Transcatheter Edge-to-Edge Repair (TEER) generally safe for humans?

TEER, including the MitraClip system, is a less invasive treatment for mitral regurgitation and is generally considered safe, though complications like the need for surgical reintervention and rare cases of device detachment have been reported. ^{2 3 5 6 7}

How is the transcatheter edge-to-edge repair (TEER) treatment for mitral valve regurgitation different from other treatments?

Transcatheter edge-to-edge repair (TEER) is unique because it is a less invasive procedure compared to traditional open-heart surgery, using a device called MitraClip to repair the mitral valve without the need for large incisions. This makes it a suitable option for patients who may not be able to undergo more invasive surgical procedures. ^{1 2 3 8 9}

Eligibility Criteria

This trial is for adults over 18 with cardiogenic shock and severe mitral valve regurgitation who are dependent on heart support drugs or ventilators. They must be able to give consent and have a heart structure suitable for the TEER procedure. Excluded are those recently revascularized, with active infections in the heart, certain neurological or pregnancy conditions, hypersensitivity to procedure meds, severe aortic disease, plans for other heart supports, prior mitral surgery except ring placement, or life-limiting comorbidities.

Inclusion Criteria

I have severe heart failure needing constant medication or mechanical support.

I am 18 years old or older.

My heart team believes I am a good candidate for a specific valve repair to improve my heart function.

Exclusion Criteria

In the opinion of the treating team, there is a significant comorbidity that would limit life expectancy in hospital

Pregnant or planning to become pregnant in the next 6 months.

My heart valve issue is due to wear and tear, and I am considered for surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vanguard Phase

Feasibility stage where 10 participants are recruited to ascertain feasibility of participant recruitment and treatment

12 months

Main Study Phase

Continuation of the study with recruitment of the remaining 134 participants, focusing on TEER and medical therapy arms

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Medical therapy
• Transcatheter edge-to-edge repair

Trial Overview The study compares two treatments: standard medical therapy versus Transcatheter edge-to-edge repair (TEER) in patients with advanced cardiogenic shock and significant mitral regurgitation. It's an open-label randomized-controlled trial aiming to see if TEER can improve outcomes better than just medication.

Participant Groups

Group I: Transcatheter edge-to-edge repair Experimental Treatment 1 Intervention

The experimental arm includes treatment in an intensive care unit with intravenous medications (e.g. vasopressors and inotropes), ventilatory support or mechanical circulatory support plus transcatheter edge-to-edge repair

Group II: Medical therapy Active Control 1 Intervention

Medical therapy includes treatment in an intensive care unit with intravenous medications (e.g. vasopressors and inotropes), ventilatory support or mechanical circulatory support.

Transcatheter edge-to-edge repair is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as MitraClip for:

• Severe mitral regurgitation in high-risk patients
• Chronic heart failure with significant mitral regurgitation

Approved in United States as MitraClip for:

• Severe mitral regurgitation in high-risk patients
• Chronic heart failure with significant mitral regurgitation

Approved in Canada as MitraClip for:

• Severe mitral regurgitation in high-risk patients
• Chronic heart failure with significant mitral regurgitation

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Findings from Research

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]

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 116 patients with functional mitral regurgitation, the use of the late-generation G4 MitraClip system resulted in greater anatomical changes in the mitral valve compared to earlier generations, including significant reductions in mitral annular size.

The G4 MitraClip led to a more pronounced decrease in the anteroposterior diameter, annular perimeter, and annular area, indicating improved efficacy in modifying mitral valve structure after transcatheter edge-to-edge repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anatomical Changes after Transcatheter Edge-to-Edge Repair in Functional MR According to MitraClip Generation. Alperi, A., Avanzas, P., Martinez, J., et al.[2023]

In a review of 11 studies involving 24,905 patients, women undergoing transcatheter edge-to-edge repair (TEER) with MitraClip experienced higher rates of periprocedural bleeding and stroke compared to men, despite having fewer baseline health issues.

There was no significant difference in procedural success or short-term mortality between sexes, but women showed lower adjusted long-term mortality rates, suggesting better long-term outcomes for women after TEER.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in outcomes of transcatheter edge-to-edge repair with MitraClip: A meta-analysis. Ya'Qoub, L., Gad, M., Faza, NN., 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]

Transcatheter edge-to-edge repair (TEER) is a minimally invasive procedure effective for treating severe mitral regurgitation (MR), but complications like single leaflet detachment (SLD) can occur, as demonstrated in a case involving an 86-year-old female patient.

This case is the first report linking electrical cardioversion to SLD after TEER, suggesting that while cardioversion is generally safe, it may lead to complications such as detachment of the mitral clip due to increased left ventricular pressure during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MitraClip detachment after electrical cardioversion: a case report. Yagel, O., Planer, D., Elitzur, Y., et al.[2023]

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 1041 patients with secondary mitral regurgitation treated with third-generation MitraClip systems, 93% achieved a reduction in mitral regurgitation to levels of MR ≤ 1+ at 30 days, which was sustained at 1-year follow-up.

Patients who achieved MR ≤ 1+ had significantly lower rates of all-cause mortality or heart failure hospitalizations (34% overall, 29.7% for MR ≤ 1+ vs. 69.6% for MR ≥ 2+), along with substantial improvements in functional status as measured by the New York Heart Association class.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter edge-to-edge repair for secondary mitral regurgitation with third-generation devices in heart failure patients - results from the Global EXPAND Post-Market study. Orban, M., Rottbauer, W., Williams, M., et al.[2023]

References

1. 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]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Anatomical Changes after Transcatheter Edge-to-Edge Repair in Functional MR According to MitraClip Generation. [2023]

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

Sex differences in outcomes of transcatheter edge-to-edge repair with MitraClip: A meta-analysis. [2022]

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

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

MitraClip detachment after electrical cardioversion: a case report. [2023]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Transcatheter edge-to-edge repair for secondary mitral regurgitation with third-generation devices in heart failure patients - results from the Global EXPAND Post-Market study. [2023]