Perkutánní nebo chirurgická oprava mitrální chlopně (PRIMARY)
Perkutánní nebo chirurgická oprava mitrálního prolapsu a regurgitace pro děti ≥65 let (PRIMÁRNÍ)
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, Spain, 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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
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 intervention 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. This study is closely integrated with the PRIMARY Ancillary Substudy (NCT07103733)
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).
Outcomes will be measured from randomization over a period of 5 years post intervention. The estimated enrollment period is 36 months, and all patients will be followed from randomization for up to 10 years post intervention for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Nelze použít
Kontakty a umístění
Studijní místa
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British Columbia
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Vancouver, British Columbia, Kanada, BC V6E 1M7
- University of British Columbia, Providence Health Care, St. Paul's Hospital
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Ontario
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London, Ontario, Kanada, ON N6A 5W9
- London Health Sciences
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Ottawa, Ontario, Kanada, K1Y 4W7
- University of Ottawa Heart Institute
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Toronto, Ontario, Kanada, M5B 1W8St
- Unity Health Toronto (St. Michael's Hospital)
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Quebec
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Québec, Quebec, Kanada, QC G1V 4G5
- Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)
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Bad Nauheim, Německo, 61231
- Kerckhoff Klinik Bad Nauheim
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Bad Rothenfelde, Německo, 49214
- Schüchtermann-Klinik Bad Rothenfelde
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Berlin, Německo, 13353
- Deutsches Herzzentrum der Charité
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Frankfurt, Německo, 60590
- Universitätsklinikum Frankfurt
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Freiburg im Breisgau, Německo, 79106
- Universitätsklinikum Freiburg
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Hamburg, Německo, 20099
- Asklepios Klinik St. Georg Hamburg
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Hamburg, Německo, 20246
- Universitätsklinikum Hamburg Eppendorf
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Heidelberg, Německo, 69120
- Universitätsklinikum Heidelberg
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Jena, Německo, 07747
- Universitätsklinikum Jena
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Kiel, Německo, 24105
- Universitätsklinikum Schleswig-Holstein Campus Kiel
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Leipzig, Německo, 04289
- Herzzentrum Leipzig
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Lübeck, Německo, 23538
- Universitätsklinikum Schleswig-Holstein Campus Lübeck
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München, Německo, 80636
- Deutsches Herzzentrum München
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Berlin-kölnische Allee
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Cologne, Berlin-kölnische Allee, Německo, 50969
- Universitätsklinikum Köln
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North Rhine-Westphalia
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Cologne, North Rhine-Westphalia, Německo, 50937
- Universitätsklinikum Köln
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Birmingham, Spojené království, B15 2TH
- University Hospitals Birmingham NHS Foundation Trust
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Bristol, Spojené království, BS1 3NU
- University Hospital Bristol and Weston NHS Foundation Trust
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Clydebank, Spojené království, G81 4DY
- Golden Jubilee University National Hospital
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Headington, Spojené království, OX3 9DU
- Oxford University Hospitals NHS Foundation Trust
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London, Spojené království, E1 8PR
- Barts Health NHS Trust
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Middlesbrough, Spojené království, TS4 3BW
- South Tees Hospitals NHS Foundation Trust
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England
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Cambridge, England, Spojené království, CB2 0AY
- Royal Papworth Hospital NHS Foundation Trust
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Leeds, England, Spojené království, LS1 3EX
- The Leeds Teaching Hospitals NHS Trust
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London, England, Spojené království, SE5 9RS
- King's College Hospital NHS Foundation Trust
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London, England, Spojené království, SE1 7EH
- St. Thomas Guy's and St Thomas' NHS Foundation Trust
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London, England, Spojené království, SW3 6NP
- Royal Brompton and Harefield Guy's and St Thomas' NHS Foundation Trust
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Manchester, England, Spojené království, M23 9LT
- Manchester University NHS Foundation Trust
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West Sussex
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Worthing, West Sussex, Spojené království, BN2 5BE
- University Hospitals Sussex NHS Foundation Trust
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California
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Los Angeles, California, Spojené státy, 90048
- Cedars Sinai Medical Center
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Los Angeles, California, Spojené státy, 90033
- Keck Hospital of the University of Southern California
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San Francisco, California, Spojené státy, 94143
- University of California San Francisco
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Stanford, California, Spojené státy, 94305
- Stanford University
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Georgia
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Atlanta, Georgia, Spojené státy, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, Spojené státy, 30322
- Emory University
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Atlanta, Georgia, Spojené státy, 30309
- Piedmont Heart Institute
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Louisiana
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New Orleans, Louisiana, Spojené státy, 70121
- Ochsner Clinic
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Maine
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Portland, Maine, Spojené státy, 04102
- Maine Medical Center
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Maryland
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Baltimore, Maryland, Spojené státy, 21287
- The Johns Hopkins Hospital
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Spojené státy, 02115
- Brigham and Women's
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Michigan
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Ann Arbor, Michigan, Spojené státy, 48109
- University of Michigan Hospital
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Missouri
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Kansas City, Missouri, Spojené státy, 64111
- Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
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New Hampshire
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Lebanon, New Hampshire, Spojené státy, 03756
- Dartmouth Hitchcock Medical Center
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New York
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Bay Shore, New York, Spojené státy, 11706
- Northwell - South Shore
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Manhasset, New York, Spojené státy, 11030
- Northwell Health - North Shore
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New York, New York, Spojené státy, 10032
- New York-Presbyterian/Columbia University Medical Center
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New York, New York, Spojené státy, 10075
- Northwell Health - Lenox Hill
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New York, New York, Spojené státy, 10065
- Weill Cornell Medicine/ New York-Presbyterian Hospital
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Staten Island, New York, Spojené státy, 10305
- Northwell Staten Island University Hospital
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North Carolina
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Durham, North Carolina, Spojené státy, 27710
- Duke University Hospital
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Ohio
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Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19104
- Hospital of the University of Pennsylvania
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South Carolina
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Charleston, South Carolina, Spojené státy, 29425
- Medical University of South Carolina
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Texas
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Dallas, Texas, Spojené státy, 75246
- Baylor, Scott and White
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Virginia
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Charlottesville, Virginia, Spojené státy, 22903
- University of Virginia Medical Center
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West Virginia
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Morgantown, West Virginia, Spojené státy, 26506
- West Virginia University Hospital
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Barcelona, Španělsko, 08036
- Hospital Clinic De Barcelona
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Madrid, Španělsko, 28040
- Hospital Clínico San Carlos
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Oviedo, Španělsko, 33011
- Hospital Central de Asturias
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Balearic Islands
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Palma de Mallorca, Balearic Islands, Španělsko, 07120
- Hospital Universitari Son Espases.
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Galacia
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Vigo, Galacia, Španělsko, 36204
- Hospital Alvaro Cunqueiro
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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 ≥60 years 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 surgical MV repair and transcatheter edge-to-edge repair (TEER) per local heart team assessment with central eligibility committee verification
- Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on local heart team assessment and central eligibility committee verification (see ACC/AHA 2020 guidelines for the management of patients with valvular heart disease)
- Patients with AF who meet an indication for a concomitant ablation procedure be included provided the local heart team and central eligibility committee decide 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:
- Non-degenerative types of primary MR (e.g., cleft leaflet)
- Secondary or functional MR
- Hypertrophic obstructive cardiomyopathy
- Presence of an IVC filter or permanent 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
- Patients with CAD requiring revascularization
- Any prior mitral valve intervention or any prior repair of atrial septal defect
- 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
- 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 survival beyond 2 years is unlikely
- Active substance abuse
- Suspected inability to adhere to follow-up
- Treatment with another investigational drug or other intervention, assessment of which has not completed the primary endpoint or that clinically interferes with the present study endpoints.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
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Aktivní komparátor: Surgical mitral valve repair
Patients who are randomized to the surgical arm will undergo mitral surgery. |
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.
Ostatní jména:
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Aktivní komparátor: 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. |
Patients will be treated with a commercially-approved edge-to-edge mitral repair device. 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/clasp 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/clasp emerges from the tip of the guide into the left atrium. The catheter is manipulated using the control handle until the clip/clasp is correctly oriented with respect to the line of coaptation of the mitral valve. The clip/clasp is opened, and advanced across the mitral valve into the left ventricle then pulled back to grasp the leaflets.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score.
Časové okno: 3 years post intervention
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All-cause mortality, valve re-intervention, hospitalizations/urgent visits for heart failure (without a blanking period), or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum of 3 years post intervention. 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. |
3 years post intervention
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Adequacy of MR correction
Časové okno: one year post intervention
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Adequacy of MR correction at one year post intervention, defined as < 2+ MR as assessed by TTE |
one year post intervention
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Kansas City Cardiomyopathy Questionnaire (KCCQ)
Časové okno: up to 10 years post intervention
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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. |
up to 10 years post intervention
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Procedure failure
Časové okno: End of procedure
|
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. |
End of procedure
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Procedure failure
Časové okno: 10 years post randomization
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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. |
10 years post randomization
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All-cause mortality
Časové okno: 5 years post randomization
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All-cause mortality through 5 years post randomization |
5 years post randomization
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All-cause mortality
Časové okno: 10 years post intervention
|
All-cause mortality from randomization through 10 years post intervention |
10 years post intervention
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Cardiovascular and non-cardiovascular mortality
Časové okno: 5 years post intervention
|
Cardiovascular and non-cardiovascular mortality from randomization through 5 years post intervention |
5 years post intervention
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Cardiovascular and non-cardiovascular mortality
Časové okno: 10 years post intervention
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Cardiovascular and non-cardiovascular mortality from randomization through 10 years post intervention |
10 years post intervention
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Valve re-interventions
Časové okno: 5 years post intervention
|
Valve re-interventions through 5 years post intervention |
5 years post intervention
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Valve re-interventions
Časové okno: 10 years post intervention
|
Valve re-interventions through 10 years post intervention |
10 years post intervention
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Serious or protocol-defined adverse events
Časové okno: 5 years post intervention
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Serious or protocol-defined adverse events, including stroke, acute kidney injury (AKI), and renal failure, through 5 years |
5 years post intervention
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MR grade
Časové okno: up to 6 years post intervention
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Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.) |
up to 6 years post intervention
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Left Ventricular Ejection Fraction (LVEF)
Časové okno: up to 6 years post intervention
|
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. |
up to 6 years post intervention
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Left Ventricular End Diastolic Dimension (LVEDD)
Časové okno: up to 6 years post intervention
|
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. |
up to 6 years post intervention
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Left Ventricular End Systolic Dimension (LVESD)
Časové okno: up to 6 years post intervention
|
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. |
up to 6 years post intervention
|
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Left Ventricular End Diastolic Volume (LVEDV)
Časové okno: up to 6 years post intervention
|
Left Ventricular end diastolic volume (LVEDV) is the volume of blood in the left ventricle at the end of the diastole or ventricular filling. |
up to 6 years post intervention
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Left Ventricular End Systolic Volume (LVESV)
Časové okno: up to 6 years post intervention
|
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. |
up to 6 years post intervention
|
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Mitral valve gradient
Časové okno: up to 6 years post intervention
|
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. |
up to 6 years post intervention
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Forward stroke volume
Časové okno: up to 6 years post intervention
|
The forward stroke volume is the volume entering the aorta. |
up to 6 years post intervention
|
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6 Minute Walk Test (6MWT)
Časové okno: up to 5 years post intervention
|
Functional status as measured by the 6MWT at yearly time intervals over 5 years. 6MT - The distance covered over a time of 6 minutes |
up to 5 years post intervention
|
|
EuroQol- 5 Dimension (EQ-5D)
Časové okno: through 10 years post intervention
|
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). |
through 10 years post intervention
|
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Length of stay (LOS)
Časové okno: through 10 years post intervention
|
Length of stay as measured by number of days hospitalized. |
through 10 years post intervention
|
|
ICU days of index hospitalization
Časové okno: through 10 years post intervention
|
Number of ICU days of index hospitalization |
through 10 years post intervention
|
|
Number and reasons for readmissions
Časové okno: through 10 years post intervention
|
Number and reasons for readmissions, including for valve re-intervention and readmissions/urgent visits for heart failure |
through 10 years post intervention
|
|
Cost
Časové okno: through 10 years post intervention
|
Costs associated with the index hospitalization as well as follow-up readmissions will be measured. |
through 10 years post intervention
|
|
Cost-effectiveness
Časové okno: through 10 years post intervention
|
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. |
through 10 years post intervention
|
|
Number of participants with stroke with disability
Časové okno: 30 days post-intervention
|
Stroke with disability is defined as a modified Rankin score of ≥ 2 and/or major bleeding (BARC Type 3b, 3c and 5) by 30 days post-intervention |
30 days post-intervention
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: Martin Leon, MD, Columbia University
- Ředitel studie: Patrick O'Gara, MD, Brigham and Women's Hospital
- Ředitel studie: Joanna Chikwe, MD, Cedars Sinai
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- STUDY-21-01246
- 5U01HL088942 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Časový rámec sdílení IPD
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.
Kritéria přístupu pro sdílení IPD
Anyone who wishes to access the data. Any purpose. Data are available indefinitely at link included in the URL field below.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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