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Trial record 1 of 2 for:    nhlbi | Recruiting Studies | mitral valve | United States
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Percutaneous or Surgical Mitral Valve Repair (PRIMARY)

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ClinicalTrials.gov Identifier: NCT05051033
Recruitment Status : Recruiting
First Posted : September 21, 2021
Last Update Posted : October 27, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Mitral Valve Regurgitation Procedure: Mitral valve repair Device: Transcatheter edge-to-edge repair Not Applicable

Detailed Description:

The primary aim of this study is to evaluate the long-term effectiveness and safety of MV TEER compared with surgical repair in patients with primary, degenerative MR. The secondary aim is to analyze the relationship between the adequacy of MR correction at one-year post randomization and longer-term clinical outcomes (death, heart failure hospitalizations/urgent care visits, valve re-interventions, and quality of life). The tertiary aim of this trial is to evaluate a range of patient-centered outcomes (quality of life, functional status, and discharge location) of transcatheter edge-to-edge MV repair compared with MV surgical repair in patients with primary, degenerative mitral regurgitation.

The patient population for this trial consists of adult patients with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible.

Because the use of the commercial edge-to-edge mitral repair device in the U.S. is approved only in patients considered to be at prohibitive risk of MV surgery by a heart team, use of such devices in this trial is considered investigational by the FDA. As such, this trial will be conducted under an Investigational Device Exemption (IDE ).

All patients with qualifying MR, who decline randomization, will be offered the option of enrollment in a parallel registry that captures their baseline risk profile and their treatment strategy received. These patients will also be asked to fill out a brief decliner survey.

Outcomes will be measured over a period of 5 years. The estimated enrollment period is 36 months, and all patients will be followed for up to 10 years post randomization for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Eligible and consented patients will be randomized 1:1 to a TEER versus surgical repair. Patient randomization will be stratified by clinical site and by surgical risk profile, namely low, intermediate, and high surgical risk. Primary effectiveness will be analyzed by intention-to-treat; that is, the patients will be grouped by their assignment at randomization whether or not they actually received the treatment to which they were assigned.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥65 Year-olds (PRIMARY)
Actual Study Start Date : January 14, 2022
Estimated Primary Completion Date : January 2028
Estimated Study Completion Date : January 2032

Arm Intervention/treatment
Active Comparator: Surgical mitral valve repair
Patients who are randomized to the surgical arm will undergo mitral surgery.
Procedure: Mitral valve repair
Patients who are randomized to the surgical arm will undergo mitral surgery. Mitral surgery will be conducted using general anesthesia and cardiopulmonary bypass. Mitral surgery may be performed via a sternotomy or a right thoracotomy approach with or without robotic assistance. Standard techniques commonly include a ring or band annuloplasty to correct and prevent annular dilatation; leaflet prolapse and redundancy may be corrected by leaflet resection techniques and / or chordal reconstruction.
Other Name: Mitral valve surgery

Active Comparator: Transcatheter edge-to-edge repair
In the transcatheter edge-to-edge repair arm, patients will be treated with a commercially-approved edge-to-edge mitral repair device.
Device: Transcatheter edge-to-edge repair
Patients will be treated with a commercially-approved edge-to-edge mitral repair device. Before using the investigational device, each patient will undergo baseline hemodynamic assessment. The steerable guide catheter (guide) is inserted into the femoral vein and advanced across the inter-atrial septum using image guided puncture. Fluoroscopic and echocardiographic guidance will be used to visualize the devices and assess the repair. The guide is positioned over the MV and the clip delivery system is inserted into the guide and positioned over the MV in accordance with the manufacturer's instructions. The delivery catheter is advanced until the clip emerges from the tip of the guide into the left atrium. The catheter is manipulated using the control handle until the clip is correctly oriented with respect to the line of coaptation of the mitral valve. The clip is opened, and advanced across the mitral valve into the left ventricle then pulled back to grasp the leaflets.
Other Name: TEER




Primary Outcome Measures :
  1. All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 3+ MR (by transthoracic echocardiogram (TTE)) composite score. [ Time Frame: 3 years post randomization ]

    Composite score of all-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 3+ MR (by transthoracic echocardiogram (TTE)) with a minimum follow-up of 3 years post randomization (including a one-month post intervention blanking period for HF hospitalizations/urgent care visits).

    Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean.



Secondary Outcome Measures :
  1. Adequacy of MR correction [ Time Frame: one year post randomization ]
    Adequacy of MR correction at one year post randomization, defined as < 2+ MR as assessed by TTE

  2. Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: up to 10 years post randomization ]
    Disease-specific quality of life as measured by the KCCQ at 6-month time intervals up to 5 years. KCCQ has 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy. The symptom frequency and symptom burden domains are merged into a total symptom score, which can be combined with the physical limitation domain to create a clinical summary score. All scores are scaled 0 to 100, with higher scores indicating better health outcome.

  3. Procedure failure [ Time Frame: 5 years post randomization ]
    Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure.

  4. Procedure failure [ Time Frame: 10 years post randomization ]
    Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure.

  5. All-cause mortality [ Time Frame: 5 years post randomization ]
    All-cause mortality through 5 years post randomization

  6. All-cause mortality [ Time Frame: 10 years post randomization ]
    All-cause mortality through 10 years post randomization

  7. Cardiovascular and non-cardiovascular mortality [ Time Frame: 5 years post randomization ]
    Cardiovascular and non-cardiovascular mortality through 5 years post randomization

  8. Cardiovascular and non-cardiovascular mortality [ Time Frame: 10 years post randomization ]
    Cardiovascular and non-cardiovascular mortality through 10 years post randomization

  9. Valve re-interventions [ Time Frame: 5 years post randomization ]
    Valve re-interventions through 5 years post randomization

  10. Valve re-interventions [ Time Frame: 10 years post randomization ]
    Valve re-interventions through 10 years post randomization

  11. Serious or protocol-defined adverse events [ Time Frame: 5 years post randomization ]
    Serious or protocol-defined adverse events, including stroke, acute kidney injury (AKI), and renal failure, through 5 years

  12. MR grade [ Time Frame: through 5 years post randomization ]
    Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.)

  13. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: through 5 years post randomization ]
    Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction.

  14. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: through 5 years post randomization ]
    Left ventricular end diastolic dimension (LVEDD) is the diameter across the left ventricle of the heart at the end of diastole, that is, when the heart muscle is maximally relaxed, and usually corresponds to its largest diameter.

  15. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: through 5 years post randomization ]
    Left ventricular end systolic dimension (LVESD) is the diameter across the left ventricle of the heart at the end of systole, that is, when the heart muscle is maximally contracted, and usually corresponds to its smallest diameter.

  16. Left Ventricular End Diastolic Volume (LVEDV) [ Time Frame: through 5 years post randomization ]
    Left Ventricular end diastolic volume (LVEDV) is the volume of blood in the left ventricle at the end of the diastole or ventricular filling.

  17. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: through 5 years post randomization ]
    Left Ventricular end systolic volume (LVESV) is the volume of blood in the left ventricle at the end of the systolic ejection phase immediately before the beginning of diastole or ventricular filling.

  18. Mitral valve gradient [ Time Frame: through 5 years post randomization ]
    The valve gradient is the difference in pressure on each side of the valve. When a valve is narrowed (a condition called stenosis), the pressure on the front of the valve builds up as blood is forced through the narrow opening. This causes a larger pressure difference between the front and back of the valve. The valve gradient can be used to determine the severity of the valve disorder.

  19. Forward stroke volume [ Time Frame: through 5 years post randomization ]
    The forward stroke volume is the volume entering the aorta.

  20. 6 Minute Walk Test (6MWT) [ Time Frame: through 5 years post randomization ]
    Functional status as measured by the 6MWT at yearly time intervals over 5 years. 6MT - The distance covered over a time of 6 minutes

  21. EuroQol- 5 Dimension (EQ-5D) [ Time Frame: through 10 years post randomization ]
    Generic QoL as measured by the EuroQol-5D (EQ-5D). The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ- 5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).

  22. Length of stay (LOS) [ Time Frame: through 10 years post randomization ]
    Length of stay as measured by number of days hospitalized.

  23. ICU days of index hospitalization [ Time Frame: through 10 years post randomization ]
    Number of ICU days of index hospitalization

  24. Number and reasons for readmissions [ Time Frame: through 10 years post randomization ]
    Number and reasons for readmissions, including for valve re-intervention and readmissions/urgent visits for heart failure

  25. Cost [ Time Frame: through 10 years post randomization ]
    Costs associated with the index hospitalization as well as follow-up readmissions will be measured.

  26. Cost-effectiveness [ Time Frame: through 10 years post randomization ]
    A cost-effectiveness analysis (CEA) comparing cumulative costs and quality-adjusted life years (QALYs) of transcatheter edge-to-edge repair vs surgical repair will be performed from U.S., Canadian, German and United Kingdom health care sector perspectives according to national guidelines.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

The patient population for this trial consists of adults with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible. Specific inclusion and exclusion criteria are listed below. All patients who meet eligibility criteria will be included in the study regardless of gender, race, or ethnicity.

Inclusion Criteria:

  • Adult patients ≥65 yrs with moderately-severe or severe (3+ or 4+/4+) primary degenerative (Carpentier type II) MR defined by transthoracic echocardiography
  • Clinical indication for MV intervention and anatomic candidate for both MV transcatheter edge-to-edge and surgical repair per local heart team assessment
  • Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on the local heart team assessment (see 2020 ACC/AHA guidelines for the management of patients with valvular heart disease)
  • Patients with AF who meet an indication for concomitant ablation may be included provided the local heart team verifies they are eligible for both catheter-based and surgical ablation.
  • Ability to perform 6-minute walk test (6MWT) and complete Kansas City Cardiomyopathy Questionnaire (KCCQ) instrument

Exclusion Criteria:

  • Other forms of primary MR (e.g., cleft leaflet, endocarditis)
  • Secondary or functional MR
  • Hypertrophic obstructive cardiomyopathy
  • Presence of an IVC filter or pacing/ICD leads that would interfere with TEER per local heart team assessment
  • Known allergic reactions to intravenous contrast
  • Febrile illness within 30-days prior to randomization
  • Any absolute contraindication to transesophageal echocardiography
  • Any contraindication to systemic heparinization including active bleeding diatheses, and heparin induced thrombocytopenia
  • Any prior MV intervention or any prior repair of atrial septal defect
  • Need for any of the following concomitant procedures: aortic valve or aortic surgery, tricuspid valve surgery
  • Patients with CAD requiring revascularization
  • Need for any emergency intervention or surgery
  • Active endocarditis
  • Hemodynamic instability defined as cardiac index <2.0 l/min/m2 or systolic blood pressure <90mmHg or need for inotropic support or any mechanical circulatory support
  • Left ventricular ejection fraction <25%
  • Intracardiac mass or thrombus
  • Co-morbid medical or oncologic condition for which local heart team believes that meaningful survival beyond 2 years is unlikely
  • Current substance abuse disorder
  • Suspected inability to adhere to follow-up
  • Treatment with another investigational drug or other intervention, assessment of which has not completed its primary endpoint or that clinically interferes with the present study endpoints.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05051033


Contacts
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Contact: Chari Ponder, RN, BSN (646) 899-8106 chari.ponder@mountsinai.org
Contact: Ellen Moquete, RN 646-734-7229 ellen.moquete@mountsinai.org

Locations
Show Show 26 study locations
Sponsors and Collaborators
Annetine Gelijns
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Study Director: Joann Chikwe, MD Cedars Sinai
Study Director: Martin Leon, MD Columbia University
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Responsible Party: Annetine Gelijns, Chair, Department of Population Health Science & Policy Edmond A. Guggenheim Professor of Health Policy Co-Director, InCHOIR, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT05051033    
Other Study ID Numbers: STUDY-21-01246
5U01HL088942 ( U.S. NIH Grant/Contract )
First Posted: September 21, 2021    Key Record Dates
Last Update Posted: October 27, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: De-identified study data sets must be submitted to the designated NHLBI Program Official no later than 3 years after the end of the clinical activity (final patient follow-up, etc.) or 2 years after the main paper of the trial has been published, whichever comes first. Data are prepared by the study coordinating center and sent to the designated PO for review prior to release.
Access Criteria: Anyone who wishes to access the data. Any purpose. Data are available indefinitely at link included in the URL field below.
URL: https://biolincc.nhlbi.nih.gov/studies/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Annetine Gelijns, Icahn School of Medicine at Mount Sinai:
surgical mitral valve repair
transcatheter edge-to-edge repair
Additional relevant MeSH terms:
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Mitral Valve Insufficiency
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases