title: Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 1: clinical trial design principles: A consensus document from the mitral valve academic research consortium.
abstract: Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York Cardiovascular Research Foundation, New York, New York gs2184@columbia.edu.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Hôpital Bichat, Paris, France.
authors.forename: Alec S
authors.initials: AS
authors.lastname: Vahanian
authors.affiliation: Mount Sinai Health System, New York, New York.
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.affiliation: The Ohio State University, Columbus, Ohio.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: SUNY Downstate Medical Center, Brooklyn, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
authors.affiliation: Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Bax
authors.affiliation: Hamburg University Cardiovascular Center, Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Schofer
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Cutlip
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Mitchell W
authors.initials: MW
authors.lastname: Krucoff
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Eugene H
authors.initials: EH
authors.lastname: Blackstone
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York Cardiovascular Research Foundation, New York, New York Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Baylor University Medical Center, Dallas, Texas.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mack
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Siegel
authors.affiliation: Baylor University Medical Center, Dallas, Texas.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Grayburn
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Maurice
authors.initials: M
authors.lastname: Enriquez-Sarano
authors.affiliation: University Hospital of Liège, Liège, Belgium.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Lancellotti
authors.affiliation: Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Erasmus University Medical Center, Rotterdam, the Netherlands. For complete information on the MVARC members and participants, please see the Online Appendix.
authors.forename: Arie Pieter
authors.initials: AP
authors.lastname: Kappetein
mesh_terms: D006328:Cardiac Catheterization / Q000379:methods*; D002986:Clinical Trials as Topic / Q000379:methods*; D035061:Control Groups; D004452:Echocardiography / Q000379:methods; D018618:Echocardiography, Doppler, Color / Q000379:methods; D023381:Endpoint Determination; D019918:Heart Valve Prosthesis Implantation / Q000379:methods*; D006801:Humans; D008944:Mitral Valve Insufficiency / Q000145:classification / Q000473:pathology / Q000601:surgery*; D061330:Multidetector Computed Tomography / Q000379:methods; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D018570:Risk Assessment
keywords: Heart failure; Mitral regurgitation; Mitral valve; Valve intervention; Valve surgery (or cardiac surgery)