Clinical trial NCT02100228: Study Of The Blood Thinner, Apixaban, For Patients Who Have An Abnormal Heart Rhythm (Atrial Fibrillation) And Expected To Have Treatment To Put Them Back Into A Normal Heart Rhythm (Cardioversion)
Official title: A Phase Iv Trial To Assess The Effectiveness Of Apixaban Compared With Usual Care Anticoagulation In Subjects With Non-valvular Atrial Fibrillation Undergoing Cardioversion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: apixaban
oral anticoagulant
non-valvular atrial fibrillation
cardioversion
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2014-03-31
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Some people can develop an abnormal heart beat known as "Atrial fibrillation" or "AF" that puts them at risk of developing clots in the heart. Those clots can travel in the blood circulation to the brain and cause a brain attack ("a stroke"). To prevent those clots forming, blood thinners (anti-coagulants) are used. Apixaban is a blood thinner that works by stopping one of the blood substances required for clotting ("Factor Xa"). It is approved and used to prevent clots forming in people with "AF". Other established blood thinners work by stopping clotting substances being made, known as "Vitamin K antagonists" or "VKAs". An example of this type is Warfarin (Coumadin). The good effects of all blood thinners are preventing clots, and they may also have bad effects of increasing the chance of bleeding. People with "AF", abnormal heart beat, may benefit from changing it back to a normal regular rhythm, known medically as "cardioversion". When this is done, people are currently most commonly treated with a "VKA" blood thinner (e.g. warfarin). The purpose of this study is to assess the good and bad effects ("efficacy" and "safety") of apixaban compared with warfarin in people with "AF" in whom an early cardioversion is planned.


Eligibility criteria: Inclusion Criteria:

* Subjects with non-valvular atrial fibrillation (as documented by electrocardiogram (ECG) at Visit 1) indicated for cardioversion and initiation of anticoagulation in accordance with the approved local label. Subjects presenting with atrial flutter with no evidence of atrial fibrillation are not eligible for enrolment.
* Age ≥18 years (Age ≥ 19 years for Korea only and Age ≥ 20 years for Japan only).
* Evidence of a personally signed and dated informed consent document indicating that the subject (or their legally-recognized representative) has been informed of all pertinent aspects of the study.
* The subject is willing to provide contact details for at least one alternate person for study staff to contact regarding their whereabouts, should the subject be lost-to-follow-up over the course of the study. (Subject to IRB/IEC approval)
* Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active.
* Subjects who are willing and able to comply with scheduled visits, treatment plan, and other study procedures.

Exclusion Criteria:

* Subjects having taken more than 48 hours of an anticoagulant (oral and/or parenteral) immediately prior to randomization.
* Contraindications to apixaban or usual care (eg, VKA) in accordance with the approved local label.
* Severe haemodynamically compromised subjects requiring emergent cardioversion.
* Patients with hemodynamically significant mitral stenosis, mechanical or biological prosthetic valve or valve repair.
* Conditions other than atrial fibrillation that require chronic anticoagulation (eg, a prosthetic heart valve).
* Simultaneous treatment with both aspirin and a thienopyridine (eg, clopidogrel, ticlopidine, prasugrel) or simultaneous treatment with both aspirin and ticagrelor.
* Pregnant females; breastfeeding females; females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product.
* Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation. Note: Subjects cannot be randomized into this study more than once.
* Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
* Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are BMS/Pfizer employees directly involved in the conduct of the trial.

Primary outcomes:
measure: Number of Participants With Acute Stroke Event
timeFrame: Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
measure: Number of Participants With Systemic Embolism Event
timeFrame: Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
measure: Number of Participants With Major Bleeding Event
timeFrame: Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
measure: Number of Participants With Clinically Relevant Non-Major Bleeding Events
timeFrame: Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
measure: Number of Participants With All Cause Death
timeFrame: Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Secondary outcomes:
measure: Time to First Attempt of Cardioversion
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
measure: Number of Participants With Different Type of Cardioversion Events
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
measure: Number of Cardioversion Attempt of Participants
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
measure: Number of Participants With Their Rhythm Status
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
measure: Duration of Hospital Stay of Participants
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
measure: Number of Participants Who Used Image Guidance Approach
timeFrame: Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brookwood Medical Center
state: Alabama
city: Birmingham
country: United States
facility: Cardiovascular Associates of the Southeast, LLC
state: Alabama
city: Avondale
country: United States
facility: Integrated Medical Services, Inc./IMS Cardiology
state: Arizona
city: Chula Vista
country: United States
facility: Chula Vista Cardiac Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Altamonte Springs
country: United States
facility: Certified Physician Investigator Research Group LLC
state: Florida
city: Altamonte Springs
country: United States
facility: Orlando Heart Specialists
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center Investigational Drug Service Pharmacy (office/storage)
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center Investigational Drug Service Pharmacy
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Hazel Crest
country: United States
facility: Chicago Medical Research, LLC
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Physician Network-Indiana Heart Physicians
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: Lexington
country: United States
facility: UK Good Samaritan Medical Office Building
state: Kentucky
city: Lexington
country: United States
facility: Good Samaritan Hospital
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Medical Center Gill Heart Institute
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Gill Heart Institute
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky HealthCare/Albert. B, Chandler Hospital
state: Kentucky
city: Louisville
country: United States
facility: Aim Clinic
state: Kentucky
city: Louisville
country: United States
facility: Cardiology Outpatient Clinic
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Clinical Trials Unit
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Louisville
country: United States
facility: Robley Rex VA Medical Center
state: Kentucky
city: Alexandria
country: United States
facility: Alexandria Cardiology Clinic
state: Louisiana
city: Worcester
country: United States
facility: University of Massachusetts Worcester Research Pharmacy
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hopsital - Allina Health System
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health Care System
state: Missouri
city: Columbia
country: United States
facility: University of Missouri Health System, Investigational Drug Serivce
state: Missouri
city: Columbia
country: United States
facility: University of Missouri Health System
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Lipid and Diabetes Research Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Hackensack
country: United States
facility: Electrophysiology Associates
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School Cardiovascular Institute
state: New Jersey
city: Brooklyn
country: United States
facility: State University of New York (SUNY) Downstate Medical Center
state: New York
city: Flushing
country: United States
facility: New York-Presbyterian/Queens
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/NY Presbyterian Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Oregon
country: United States
facility: ProMedica Physicians Cardiology
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Physicians Cardiology
state: Ohio
city: Tulsa
country: United States
facility: Hillcrest Medical Center Pharmacy
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute at Hillcrest Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Bristol
country: United States
facility: Cardiology Consultants of Philadelphia
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Medical Specialist Association
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Healthcare Network
state: Pennsylvania
city: Yardley
country: United States
facility: Cardiology consultants of Philadelphia
state: Pennsylvania
city: Beaumont
country: United States
facility: Baptist Hospital of Southeast Texas - Beaumont
state: Texas
city: Beaumont
country: United States
facility: Southeast Texas Cardiology Associates II, L.L.P.
state: Texas
city: Beaumont
country: United States
facility: Southeast Texas Cardiology Associates II, L.L.P
state: Texas
city: Beaumont
country: United States
facility: Southeast Texas Clinical Research Center
state: Texas
city: Layton
country: United States
facility: Utah Cardiology, PC
state: Utah
city: Midlothian
country: United States
facility: Cardiovascular Associates of Virginia-Bon Secours St. Mary's Hospital
state: Virginia
city: Midlothian
country: United States
facility: St. Francis Medical Center
state: Virginia
city: Richmond
country: United States
facility: Dominion Cardiovascular Specialists PLLC
state: Virginia
city: Heusden-Zolder
country: Belgium
facility: Sint-Franciskusziekenhuis
state: Limburg
city: Gent
country: Belgium
facility: University Hospital Ghent
state: Oost-vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: Brasschaat
country: Belgium
facility: Algemeen Ziekenhuis Klina
city: Gilly
country: Belgium
facility: Grand Hopital de Charleroi asbl
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis-Campus Virga Jesse
city: Roeselare
country: Belgium
facility: AZ Delta
city: Yvoir
country: Belgium
facility: Cliniques Universitatires UCL Mont-Godinne
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal -ICM / Montreal Heart Institute-MHI
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Silkeborg
country: Denmark
facility: Regionshospitalet Silkeborg
state: Midtjylland
city: Slagelse
country: Denmark
facility: Slagelse Hospital
state: Sjaelland
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Viborg
country: Denmark
facility: Regionhospitalet Viborg
city: Ludwigsburg
country: Germany
facility: Cardio Centrum Ludwigsburg Bietigheim
state: Baden-württemberg
city: Berlin
country: Germany
facility: Charitè Campus Mitte/ Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie
city: Berlin
country: Germany
facility: Vivantes -Netzwerk fuer Gesundheit GmbH - Klinikum Neukoelln
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Vivantes Netzwerk fuer Gesundhelt GmbH, Humboldt Klinikum
city: Bremen
country: Germany
facility: Klinikum Links der Weser gGmbH
city: Chemnitz
country: Germany
facility: Medizinisches Versorgungszentrum am Küchwald GmbH
city: Coburg
country: Germany
facility: Klinikum Coburg gGmbH
city: Dresden
country: Germany
facility: Zentrum fuer klinische Pruefungen in der Facharztzentrum Dresden-Neustadt GbR
city: Dresden
country: Germany
facility: Praxisklinik Herz und Gefäße
city: Duisburg
country: Germany
facility: Johanniter-Krankenhaus Rheinhausen GmbH/ Klinik fuer Kardiologie
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Frankfurt/Main
country: Germany
facility: Johann-Wolfgang Goethe-Universitaet
city: Greifswald
country: Germany
facility: Universitatsmedizin Greifswald
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf, Universitäres Herzzentrum Hamburg GmbH
city: Heidelberg
country: Germany
facility: Unklinik Heidelberg
city: Heidenheim
country: Germany
facility: Klinikum Heidenheim
city: Ingolstadt
country: Germany
facility: Klinikum Ingolstadt/ Medizinische Klinik I und IV
city: Leipzig
country: Germany
facility: Cardiocenter Rhythmologie
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH/ Abteilung für Rhythmologie
city: Mainz
country: Germany
facility: Katholisches Klinikum Mainz
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Moenchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Villingen-Schwenningen
country: Germany
facility: Prof. Dr. med. Werner Jung,Schwarzwald - Baar Klinikum
city: Warendorf
country: Germany
facility: Josephs-Hospital Warendorf
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Ashkelon
country: Israel
facility: Barzilai Medical Center (Cardiology)
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Centre, Soroka Medical center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Mount Scopus
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Safed
country: Israel
facility: ZIV Medical Center
city: Tel Aviv
country: Israel
facility: Clinical Trial Network Services
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tiberias
country: Israel
facility: The Baruch Padeh Medical Center
city: Acquaviva Delle Fonti (BA)
country: Italy
facility: Ospedale Generale Regionale F. Miulli-Ente Ecclesiastico
state: Bari
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
state: Lazio
city: Milano
country: Italy
facility: I.R.C.C.S. Ospedale San Raffaele S.r.l.
state: Lombardia
city: Torrette Di Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
state: Marche
city: Arezzo
country: Italy
facility: Presidio Ospedaliero San Donato
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi, Medicina e Cardiologia Geriatrica
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Roma
country: Italy
facility: DAI Malattie Cardiovascolari e Respiratorie
city: Seto
country: Japan
facility: Tosei General Hospital
state: Aichi
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center
state: Tokyo
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A Unversity Hospital
city: Daegu-si
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Deagu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital, cardiology and Electrophysiology
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul ST.MARY'S Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital, Division of Cardiology
city: Brasov
country: Romania
facility: Brasov Emergency Clinical County Hospital
city: Bucharest
country: Romania
facility: "Prof. Dr.C.C. lliescu" Emergency Institute for Cardiovascular Diseases Bucharest
city: Bucharest
country: Romania
facility: Bucharest Emergency University Hospital
city: Cluj-Napoca
country: Romania
facility: Cluj-Napoca Rehabilitation Clinical Hospital
city: Craiova
country: Romania
facility: Craiova Emergency Clinical County Hospital
city: Iasi
country: Romania
facility: Prof.Dr.George I.M. Georgescu Cardiovascular Diseases Institute
city: Targu Mures
country: Romania
facility: Cardio Med SRL
city: Tirgu Mures
country: Romania
facility: Tirgu Mures Emergency Clinical County Hospital
city: San Juan
country: Spain
facility: Hospital Universitario San Juan de Alicante
state: Alicante
city: Torrelavega
country: Spain
facility: Hospital de Sierrallana
state: Cantabria
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa Hospital de Terrassa
state: Cataluna
city: San Sebastián De Los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
state: Madrid
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus AB
state: Sodermanlands LAN
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset I Uppsala/ Kardiologikliniken
state: Uppsala IAN
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: Linkopings Universitetssjukhus Kardiologkliniken
city: Orebro
country: Sweden
facility: Universitetssjukhuset i Orebro/ Hjartmottagningen
city: Skelleftea
country: Sweden
facility: Skelleftea Country Hospital
city: Stockholm
country: Sweden
facility: Sodersjukhuset
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ezekowitz MD, Pollack CV Jr, Halperin JL, England RD, VanPelt Nguyen S, Spahr J, Sudworth M, Cater NB, Breazna A, Oldgren J, Kirchhof P. Apixaban compared to heparin/vitamin K antagonist in patients with atrial fibrillation scheduled for cardioversion: the EMANATE trial. Eur Heart J. 2018 Aug 21;39(32):2959-2971. doi: 10.1093/eurheartj/ehy148.