Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients

NCT ID: NCT02701283

Last Updated: 2025-10-21

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

2223 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2026-03-31

Brief Summary

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The study objective is to demonstrate that the safety and effectiveness of the Medtronic TAVR system as measured by rates of all-cause mortality or disabling stroke at two years is noninferior to SAVR in the treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR.

The purpose of the expanded use addendum to the Medtronic TAVR in Low Risk Patients Trial protocol is to conclude the randomized phase of the trial and initiate the single-arm, non-randomized, continued access phase of the trial.

Detailed Description

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Multi-center, international, prospective, randomized, interventional, pre-market.

Subjects will be randomized on 1:1 basis to either TAVR with the Medtronic TAVR system or to SAVR. Patients will be seen at pre and post-procedure, discharge, 30 days, 6 months, 1 year, 18 months, and annually through 10 years.

The expanded use addendum is a multi-center, prospective, non-randomized continued access trial. All heart team approved subjects will be assigned to TAVR with the Medtronic TAVR system. Patients will be seen at pre and post-procedure, discharge, 30 days, and annually through 10 years. Enrollment is expected not to exceed 3660 attempted implants in the United States.

Conditions

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Aortic Valve Stenosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Medtronic Transcatheter Aortic Valve Replacement Systems

Treatment of Aortic Stenosis with the Medtronic CoreValve System Transcatheter Aortic Valve Implantation (TAVI) device or the Medtronic Corevalve Evolut R System Transcatheter Aortic Valve Implantation (TAVI)

Group Type EXPERIMENTAL

Medtronic Transcatheter Aortic Valve Replacement Systems

Intervention Type DEVICE

Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with Medtronic TAVR Systems

Surgical Aortic Valve Replacement (SAVR)

Treatment of Aortic Stenosis with commercial Surgical Aortic Valve Replacement (SAVR)

Group Type ACTIVE_COMPARATOR

Surgical Aortic Valve Replacement (SAVR)

Intervention Type DEVICE

Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with a commercially approved surgical bioprothesis

Interventions

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Medtronic Transcatheter Aortic Valve Replacement Systems

Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with Medtronic TAVR Systems

Intervention Type DEVICE

Surgical Aortic Valve Replacement (SAVR)

Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with a commercially approved surgical bioprothesis

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Severe aortic stenosis, defined as follows:

1. For symptomatic patients:

Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), OR mean gradient ≥40 mmHg, OR Maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest
2. For asymptomatic patients:

* Very severe aortic stenosis with an aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND maximal aortic velocity ≥5.0 m/sec , or mean gradient ≥60 mmHg by transthoracic echocardiography at rest, OR
* Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND a mean gradient ≥40 mmHg or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR
* Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND mean gradient ≥40 mmHg, or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND a left ventricular ejection fraction \<50%.
2. Documented heart team agreement of low risk for SAVR, where low risk is defined as predicted risk of mortality for SAVR \<3% at 30 days per multidisciplinary local heart team assessment.
3. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria

1. Any condition considered a contraindication for placement of a bioprosthetic valve (eg, subject is indicated for mechanical prosthetic valve).
2. A known hypersensitivity or contraindication to any of the following that cannot be adequately pre-medicated:

1. aspirin or heparin (HIT/HITTS) and bivalirudin
2. ticlopidine and clopidogrel
3. Nitinol (titanium or nickel)
4. contrast media
3. Blood dyscrasias as defined: leukopenia (WBC \<1000 mm3), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
4. Ongoing sepsis, including active endocarditis.
5. Any percutaneous coronary or peripheral interventional procedure with a bare metal stent within 30 days prior to randomization, or drug eluting stent performed within 180 days prior to randomization.
6. Multivessel coronary artery disease with a Syntax score \>22 and/or unprotected left main coronary artery.
7. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
8. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
9. Recent (within 2 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
10. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
11. Subject refuses a blood transfusion.
12. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
13. Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions.
14. Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams.
15. Currently participating in an investigational drug or another device trial (excluding registries).
16. Evidence of an acute myocardial infarction ≤30 days before the trial procedure due to unstable coronary artery disease (WHO criteria).
17. Need for emergency surgery for any reason.
18. Subject is pregnant or breast feeding.
19. Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable
20. Pre-existing prosthetic heart valve in any position.
21. Severe mitral regurgitation amenable to surgical replacement or repair.
22. Severe tricuspid regurgitation amenable to surgical replacement or repair.
23. Moderate or severe mitral stenosis amenable to surgical replacement or repair.
24. Hypertrophic obstructive cardiomyopathy with left ventricular outflow gradient.
25. Bicuspid aortic valve verified by echocardiography, MDCT, or MRI.
26. Prohibitive left ventricular outflow tract calcification.
27. Sinus of Valsalva diameter unsuitable for placement of the self-expanding bioprosthesis.
28. Aortic annulus diameter of \<18 or \>30 mm.
29. Significant aortopathy requiring ascending aortic replacement.

For transfemoral or transaxillary (subclavian) access:
30. Access vessel mean diameter \<5.0 mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter \<5.5 mm for Evolut 34R mm or Evolut PRO TAV. However, for transaxillary (subclavian) access in patients with a patent LIMA, access vessel mean diameter \<5.5mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter \<6.0 mm for the Evolut 34R or Evolut PRO TAV.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medtronic Cardiovascular

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

John K. Forrest, MD

Role: PRINCIPAL_INVESTIGATOR

Yale New Haven Hospital

Locations

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Abrazo Arizona Heart Hospital

Phoenix, Arizona, United States

Site Status

Scripps Memorial Hospital La Jolla

La Jolla, California, United States

Site Status

University of Southern California University Hospital

Los Angeles, California, United States

Site Status

El Camino Hospital

Mountain View, California, United States

Site Status

Mercy General Hospital

Sacramento, California, United States

Site Status

Los Robles Hospital & Medical Center

Thousand Oaks, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Morton Plant Hospital

Clearwater, Florida, United States

Site Status

Delray Medical Center

Delray Beach, Florida, United States

Site Status

HealthPark Medical Center

Fort Myers, Florida, United States

Site Status

University of Miami Hospital

Miami, Florida, United States

Site Status

Tallahassee Research Institute, Inc.

Tallahassee, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Saint Vincent Heart Center of Indiana

Indianapolis, Indiana, United States

Site Status

Mercy Medical Center

Des Moines, Iowa, United States

Site Status

The University of Kansas Hospital

Kansas City, Kansas, United States

Site Status

Jewish Hospital

Louisville, Kentucky, United States

Site Status

Terrebonne General Medical Center

Houma, Louisiana, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

MedStar Union Memorial Hospital

Baltimore, Maryland, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Spectrum Health Hospitals

Grand Rapids, Michigan, United States

Site Status

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Mercy Hospital

Springfield, Missouri, United States

Site Status

Saint Francis Hospital

East Hills, New York, United States

Site Status

Saint Joseph's Hospital Health Center

Liverpool, New York, United States

Site Status

Northwell Health

Manhasset, New York, United States

Site Status

The Mount Sinai Hospital

New York, New York, United States

Site Status

Strong Memorial Hospital

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Sanford Medical Center

Fargo, North Dakota, United States

Site Status

Good Samaritan Hospital

Cincinnati, Ohio, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

Site Status

Geinsinger Medical Center

Danville, Pennsylvania, United States

Site Status

Pinnacle Health

Harrisburg, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

Paramount Heart

Villanova, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor Jack and Jane Hamilton Heart and Vascular Hospital

Dallas, Texas, United States

Site Status

Baylor Saint Luke's Medical Center

Houston, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

Methodist Hospital San Antonio

San Antonio, Texas, United States

Site Status

University Hospital Salt Lake City Utah

Salt Lake City, Utah, United States

Site Status

The University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Saint Mary's Hospital

Richmond, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Saint Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Fiona Stanley Hospital (FSH)

Murdoch, Western Australia, Australia

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Toronto General Health Hospital

Toronto, Ontario, Canada

Site Status

Glen Royal Victoria (McGill)

Montreal, Quebec, Canada

Site Status

IUCPQ

Québec, Quebec, Canada

Site Status

Montreal Heart

Montreal, , Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, , Canada

Site Status

Centre Hospitalier Régional Universitaire de Lille

Lille, , France

Site Status

L'Hôpital Privé Jacques Cartier Massy

Massy, , France

Site Status

Clinique Pasteur

Toulouse, , France

Site Status

Kokura Memorial Hospital

Kitakyushu, Fokuoka, Japan

Site Status

Sapporo Higashi Tokushukai Hospital

Sapporo, Hokkaido, Japan

Site Status

Teikyo University Hospital

Tokyo, Itabashi-Ku, Japan

Site Status

Shonan Kamakura General Hospital

Kamakura, Kanagawa, Japan

Site Status

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Site Status

National Cerebral and Cardiovasclular Center

Suita, Osaka, Japan

Site Status

The University of Osaka Hospital

Suita, Osaka, Japan

Site Status

Sakakibara Heart Institute

Fuchū, Tokyo, Japan

Site Status

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status

St. Antonius Hospital Nieuwegein

Nieuwegein, , Netherlands

Site Status

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Countries

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United States Australia Canada France Japan Netherlands New Zealand

References

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Forrest JK, Yakubov SJ, Deeb GM, Gada H, Mumtaz MA, Ramlawi B, Bajwa T, Crouch J, Merhi W, Wai Sang SL, Kleiman NS, Petrossian G, Robinson NB, Sorajja P, Iskander A, Berthoumieu P, Tchetche D, Feindel C, Horlick EM, Saito S, Oh JK, Jung Y, Reardon MJ; Low Risk Trial Investigators. 5-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2025 Apr 22;85(15):1523-1532. doi: 10.1016/j.jacc.2025.03.004. Epub 2025 Mar 30.

Reference Type DERIVED
PMID: 40158212 (View on PubMed)

Butala NM, Lalani C, Tale A, Song Y, Kolte D, Baron S, Strom J, Cohen DJ, Yeh RW. Use of Claims to Assess Outcomes and Treatment Effects in the Evolut Low Risk Trial. Circ Cardiovasc Interv. 2025 Jan;18(1):e014592. doi: 10.1161/CIRCINTERVENTIONS.124.014592. Epub 2025 Jan 21.

Reference Type DERIVED
PMID: 39836743 (View on PubMed)

Modine T, Tchetche D, Van Mieghem NM, Deeb GM, Chetcuti SJ, Yakubov SJ, Sorajja P, Gada H, Mumtaz M, Ramlawi B, Bajwa T, Crouch J, Teirstein PS, Kleiman NS, Iskander A, Bagur R, Chu MWA, Berthoumieu P, Sudre A, Adrichem R, Ito S, Huang J, Popma JJ, Forrest JK, Reardon MJ. Three-Year Outcomes Following TAVR in Younger (<75 Years) Low-Surgical-Risk Severe Aortic Stenosis Patients. Circ Cardiovasc Interv. 2024 Nov;17(11):e014018. doi: 10.1161/CIRCINTERVENTIONS.124.014018. Epub 2024 Oct 18.

Reference Type DERIVED
PMID: 39421943 (View on PubMed)

Klautz RJM, Rao V, Reardon MJ, Deeb GM, Dagenais F, Moront MG, Little SH, Labrousse L, Patel HJ, Ito S, Li S, Sabik JF 3rd, Oh JK. Examining the typical hemodynamic performance of nearly 3000 modern surgical aortic bioprostheses. Eur J Cardiothorac Surg. 2024 May 3;65(5):ezae122. doi: 10.1093/ejcts/ezae122.

Reference Type DERIVED
PMID: 38710669 (View on PubMed)

Tang GHL, Spencer J, Rogers T, Grubb KJ, Gleason P, Gada H, Mahoney P, Dauerman HL, Forrest JK, Reardon MJ, Blanke P, Leipsic JA, Abdel-Wahab M, Attizzani GF, Puri R, Caskey M, Chung CJ, Chen YH, Dudek D, Allen KB, Chhatriwalla AK, Htun WW, Blackman DJ, Tarantini G, Zhingre Sanchez J, Schwartz G, Popma JJ, Sathananthan J. Feasibility of Coronary Access Following Redo-TAVR for Evolut Failure: A Computed Tomography Simulation Study. Circ Cardiovasc Interv. 2023 Nov;16(11):e013238. doi: 10.1161/CIRCINTERVENTIONS.123.013238. Epub 2023 Nov 21.

Reference Type DERIVED
PMID: 37988439 (View on PubMed)

Grubb KJ, Shekiladze N, Spencer J, Perdoncin E, Tang GHL, Xie J, Lisko J, Sanchez JZ, Lucas LM, Sathananthan J, Rogers T, Deeb GM, Fukuhara S, Blanke P, Leipsic JA, Forrest JK, Reardon MJ, Gleason P. Feasibility of redo-TAVI in self-expanding Evolut valves: a CT analysis from the Evolut Low Risk Trial substudy. EuroIntervention. 2023 Jul 17;19(4):e330-e339. doi: 10.4244/EIJ-D-22-01125.

Reference Type DERIVED
PMID: 37067193 (View on PubMed)

Forrest JK, Deeb GM, Yakubov SJ, Gada H, Mumtaz MA, Ramlawi B, Bajwa T, Teirstein PS, DeFrain M, Muppala M, Rutkin BJ, Chawla A, Jenson B, Chetcuti SJ, Stoler RC, Poulin MF, Khabbaz K, Levack M, Goel K, Tchetche D, Lam KY, Tonino PAL, Ito S, Oh JK, Huang J, Popma JJ, Kleiman N, Reardon MJ; Low Risk Trial Investigators. 3-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2023 May 2;81(17):1663-1674. doi: 10.1016/j.jacc.2023.02.017. Epub 2023 Mar 5.

Reference Type DERIVED
PMID: 36882136 (View on PubMed)

Ramlawi B, Deeb GM, Yakubov SJ, Markowitz AH, Hughes GC, Kiaii RB, Huang J, Kleiman NS, Reardon MJ. Mechanisms of Death in Low-Risk Patients After Transcatheter or Surgical Aortic Valve Replacement. Cardiovasc Revasc Med. 2022 Sep;42:1-5. doi: 10.1016/j.carrev.2022.03.027. Epub 2022 Mar 29.

Reference Type DERIVED
PMID: 35398007 (View on PubMed)

Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, Mumtaz M, Gada H, O'Hair D, Bajwa T, Sorajja P, Heiser JC, Merhi W, Mangi A, Spriggs DJ, Kleiman NS, Chetcuti SJ, Teirstein PS, Zorn GL 3rd, Tadros P, Tchetche D, Resar JR, Walton A, Gleason TG, Ramlawi B, Iskander A, Caputo R, Oh JK, Huang J, Reardon MJ. 2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. J Am Coll Cardiol. 2022 Mar 8;79(9):882-896. doi: 10.1016/j.jacc.2021.11.062.

Reference Type DERIVED
PMID: 35241222 (View on PubMed)

Lanz J, Reardon MJ, Pilgrim T, Stortecky S, Deeb GM, Chetcuti S, Yakubov SJ, Gleason TG, Huang J, Windecker S. Incidence and Outcomes of Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement. J Am Heart Assoc. 2021 Oct 5;10(19):e020368. doi: 10.1161/JAHA.120.020368. Epub 2021 Sep 28.

Reference Type DERIVED
PMID: 34581194 (View on PubMed)

Blanke P, Leipsic JA, Popma JJ, Yakubov SJ, Deeb GM, Gada H, Mumtaz M, Ramlawi B, Kleiman NS, Sorajja P, Askew J, Meduri CU, Kauten J, Melnitchouk S, Inglessis I, Huang J, Boulware M, Reardon MJ; Evolut Low Risk LTI Substudy Investigators. Bioprosthetic Aortic Valve Leaflet Thickening in the Evolut Low Risk Sub-Study. J Am Coll Cardiol. 2020 May 19;75(19):2430-2442. doi: 10.1016/j.jacc.2020.03.022. Epub 2020 Mar 28.

Reference Type DERIVED
PMID: 32234463 (View on PubMed)

Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O'Hair D, Bajwa T, Heiser JC, Merhi W, Kleiman NS, Askew J, Sorajja P, Rovin J, Chetcuti SJ, Adams DH, Teirstein PS, Zorn GL 3rd, Forrest JK, Tchetche D, Resar J, Walton A, Piazza N, Ramlawi B, Robinson N, Petrossian G, Gleason TG, Oh JK, Boulware MJ, Qiao H, Mugglin AS, Reardon MJ; Evolut Low Risk Trial Investigators. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1706-1715. doi: 10.1056/NEJMoa1816885. Epub 2019 Mar 16.

Reference Type DERIVED
PMID: 30883053 (View on PubMed)

Leipsic J, Bax JJ, Webb JG, Martin R, Blanke P. Trials Testing the Value of Imaging Use in Valve Disease and in Transcatheter Valvular Interventions. JACC Cardiovasc Imaging. 2017 Mar;10(3):286-295. doi: 10.1016/j.jcmg.2016.09.031.

Reference Type DERIVED
PMID: 28279376 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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10234430Doc

Identifier Type: -

Identifier Source: org_study_id

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