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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if transcatheter edge-to-edge repair (TEER), a common heart treatment, can aid recovery in individuals with severe heart issues and mitral regurgitation more effectively than medication alone. Participants will receive either the TEER procedure or standard medical treatment, which includes medications and intensive care support. The trial seeks individuals who have been in an ICU for serious heart problems and experience impaired heart valve function, resulting in complications like fluid buildup in the lungs. As an unphased trial, this study provides a unique opportunity to contribute to medical knowledge and potentially enhance treatment options for future patients.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transcatheter edge-to-edge repair (TEER) for mitral valve problems is generally safe. Studies have found that five years after treatment, patients experience fewer hospital visits for heart failure and a reduced risk of death. In another study, the procedure succeeded in 86% of patients, with a low death rate within 30 days. These results suggest that TEER is well-tolerated and effective for many individuals with heart issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcatheter edge-to-edge repair for mitral valve regurgitation because it offers a less invasive alternative to traditional open-heart surgery. Unlike standard treatments that often involve major surgery, this technique uses a catheter to repair the mitral valve, which can mean a faster recovery and fewer complications. Additionally, it combines conventional medical therapy with cutting-edge mechanical support, potentially improving outcomes for patients who are too high-risk for surgery. This innovative approach could significantly enhance patient care by providing effective treatment options with reduced downtime.

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

Research shows that transcatheter edge-to-edge repair (TEER), a procedure available to participants in this trial, effectively repairs a leaky heart valve, known as mitral valve regurgitation, especially in individuals with long-term heart failure. One study found that TEER reduced the leak's severity to very low levels in over 90% of patients after one year. Another study showed that TEER led to fewer hospital visits for heart failure and lowered death rates over five years. While most research focuses on chronic heart failure, these results suggest that TEER might also benefit those with mitral valve issues during a heart-related shock. The device used in TEER is highly reliable, with nearly all procedures completed successfully. Meanwhile, another arm of this trial involves medical therapy, including treatment in an intensive care unit with intravenous medications, ventilatory support, or mechanical circulatory support. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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.

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

Participants or substitute decision maker is able and willing to provide written informed consent

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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]

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 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) 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 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 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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1050173825000258

Transcatheter edge-to-edge repair for mitral regurgitation Currently, the longest available follow-up after M-TEER includes the 5-year outcomes from the EVEREST II and COAPT trials, along with a 5-year analysis from a ...

2. jacc.org jacc.org/doi/10.1016/j.jcin.2023.09.029

1-Year Outcomes With Fourth-Generation Mitral Valve ... M-TEER with the fourth-generation M-TEER device was safe and effective at 1 year, with durable reductions in MR severity to ≤1+ in more than 90% of patients.

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.039285

Mitral Valve Transcatheter Edge‐to‐Edge Repair or ... The present study encompasses all available randomized data on M‐TEER at the longest follow‐up and shows likely reductions in all‐cause death, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11584375/

Outcomes of mitral transcatheter edge to edge repair with ... The device was implanted successfully in all but one patient with technical success rate of 98.4 %. The average number of clips per patient was ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2300213

Five-Year Follow-up after Transcatheter Repair ... Transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399131/

Efficacy and Safety of Transcatheter Mitral Valve Edge-to ... At the 1-year follow-up, mortality was 12.7%. The composite of death or hospitalization for HF was reduced from 50.7% of patients in the year prior to M-TEER, ...

7. jacc.org jacc.org/doi/10.1016/j.jchf.2025.102565

Transcatheter Edge-to-Edge Repair in Secondary Mitral ... Procedural outcomes were similarly safe and effective in the 2 groups (Table 2). Acute procedural success rates were consistently high and similar in both ...

8. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.034932

Transcatheter Edge‐to‐Edge Repair for Severe Mitral ... Device success was achieved in 86% (95% CI, 85%–87%) and mitral regurgitation ≤2+ in 89% (95% CI: 88%–90%). The 30‐day all‐cause mortality rate ...