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)
EMANATE
A Phase Iv Trial To Assess The Effectiveness Of Apixaban Compared With Usual Care Anticoagulation In Subjects With Non-valvular Atrial Fibrillation Undergoing Cardioversion
4 other identifiers
interventional
1,500
12 countries
165
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 atrial-fibrillation
Started Jul 2014
165 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 5, 2014
CompletedFirst Posted
Study publicly available on registry
March 31, 2014
CompletedStudy Start
First participant enrolled
July 14, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 8, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 8, 2017
CompletedResults Posted
Study results publicly available
April 10, 2018
CompletedMay 23, 2018
May 1, 2018
2.6 years
February 5, 2014
January 17, 2018
May 21, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Number of Participants With Acute Stroke Event
An acute stroke was defined as a new, important neurological insufficiency of rapid onset that lasted for at least 24 hours and that was not due to a readily identifiable non-vascular cause (like brain tumor or trauma).
Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Number of Participants With Systemic Embolism Event
Systemic embolism occurred in participant when there was a clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), which was supported by evidence of embolism from surgical specimens, autopsy, angiography, or other objective testing.
Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Number of Participants With Major Bleeding Event
Major bleeding was defined as clinically evident bleeding that was accompanied by one or more of the following: a decrease in hemoglobin of 2 gram per deciliter or more, a transfusion of 2 or more units of packed red blood cells, bleeding that was fatal or bleeding that occurred in at least one of the following critical sites: intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed was not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal.
Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Number of Participants With Clinically Relevant Non-Major Bleeding Events
Clinically relevant non-major bleeding was defined as the clinically evident bleeding that consisted of any bleeding that compromised hemodynamics, that led to hospitalization, subcutaneous hematoma larger than 25/100 centimeter square if there was a traumatic cause, intramuscular hematoma documented by ultrasonography, epistaxis, gingival bleeding occurred spontaneously, hematuria that was macroscopic and was spontaneous, macroscopic gastrointestinal hemorrhage included at least one episode of melena or hematemesis, rectal blood loss, hemoptysis or any other bleeding type considered to have clinical consequences for a participant, such as medical intervention, the need for unscheduled contact with a physician, or temporary cessation of a study drug, or associated with pain or impairment of activities of daily life.
Baseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Number of Participants With All Cause Death
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 (6)
Time to First Attempt of Cardioversion
Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Number of Participants With Different Type of Cardioversion Events
Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Number of Cardioversion Attempt of Participants
Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Number of Participants With Their Rhythm Status
Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Duration of Hospital Stay of Participants
Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
- +1 more secondary outcomes
Study Arms (2)
Apixaban
EXPERIMENTALParenteral heparin and/or oral Vitamin K antagonist
ACTIVE COMPARATORParenteral heparin and/or locally used oral Vitamin K antagonist e.g. warfarin (excludes other novel oral anticoagulants)
Interventions
Parenteral heparin and/or locally used oral Vitamin K antagonist e.g. warfarin (excludes other novel oral anticoagulants)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
- Bristol-Myers Squibbcollaborator
Study Sites (165)
Brookwood Medical Center
Birmingham, Alabama, 35209, United States
Cardiovascular Associates of the Southeast, LLC
Birmingham, Alabama, 35243, United States
Integrated Medical Services, Inc./IMS Cardiology
Avondale, Arizona, 85392, United States
Chula Vista Cardiac Center
Chula Vista, California, 91910, United States
Hartford Hospital
Hartford, Connecticut, 06102, United States
Certified Physician Investigator Research Group LLC
Altamonte Springs, Florida, 32714, United States
Orlando Heart Specialists
Altamonte Springs, Florida, 32714, United States
The University of Chicago Medical Center Investigational Drug Service Pharmacy (office/storage)
Chicago, Illinois, 60637, United States
The University of Chicago Medical Center Investigational Drug Service Pharmacy
Chicago, Illinois, 60637, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Chicago Medical Research, LLC
Hazel Crest, Illinois, 60429, United States
Franciscan Physician Network-Indiana Heart Physicians
Indianapolis, Indiana, 46237, United States
Franciscan St. Francis Health
Indianapolis, Indiana, 46237, United States
UK Good Samaritan Medical Office Building
Lexington, Kentucky, 40508-2678, United States
Good Samaritan Hospital
Lexington, Kentucky, 40508-3008, United States
University of Kentucky Medical Center Gill Heart Institute
Lexington, Kentucky, 40536-0200, United States
University of Kentucky Gill Heart Institute
Lexington, Kentucky, 40536, United States
University of Kentucky HealthCare/Albert. B, Chandler Hospital
Lexington, Kentucky, 40536, United States
Aim Clinic
Louisville, Kentucky, 40202, United States
Cardiology Outpatient Clinic
Louisville, Kentucky, 40202, United States
University of Louisville Clinical Trials Unit
Louisville, Kentucky, 40202, United States
University of Louisville Hospital
Louisville, Kentucky, 40202, United States
Robley Rex VA Medical Center
Louisville, Kentucky, 40206, United States
Alexandria Cardiology Clinic
Alexandria, Louisiana, 71301, United States
University of Massachusetts Worcester Research Pharmacy
Worcester, Massachusetts, 01655, United States
University of Massachusetts Worcester
Worcester, Massachusetts, 01655, United States
William Beaumont Hospital
Royal Oak, Michigan, 48073, United States
Abbott Northwestern Hopsital - Allina Health System
Minneapolis, Minnesota, 55407, United States
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407, United States
University of Missouri Health Care System
Columbia, Missouri, 65212, United States
University of Missouri Health System, Investigational Drug Serivce
Columbia, Missouri, 65212, United States
University of Missouri Health System
Columbia, Missouri, 65212, United States
Saint Luke's Lipid and Diabetes Research Center
Kansas City, Missouri, 64111, United States
Mercy Hospital St. Louis
St Louis, Missouri, 63141, United States
Electrophysiology Associates
Hackensack, New Jersey, 07601, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08901, United States
Rutgers Robert Wood Johnson Medical School Cardiovascular Institute
New Brunswick, New Jersey, 08901, United States
State University of New York (SUNY) Downstate Medical Center
Brooklyn, New York, 11203, United States
New York-Presbyterian/Queens
Flushing, New York, 11355, United States
Columbia University Medical Center/NY Presbyterian Hospital
New York, New York, 10032, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
ProMedica Physicians Cardiology
Oregon, Ohio, 43616, United States
ProMedica Toledo Hospital
Toledo, Ohio, 43606, United States
ProMedica Physicians Cardiology
Toledo, Ohio, 43615, United States
Hillcrest Medical Center Pharmacy
Tulsa, Oklahoma, 74104, United States
Oklahoma Heart Institute at Hillcrest Medical Center
Tulsa, Oklahoma, 74104, United States
Oklahoma Heart Institute
Tulsa, Oklahoma, 74104, United States
Cardiology Consultants of Philadelphia
Bristol, Pennsylvania, 19007, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010, United States
Bryn Mawr Medical Specialist Association
Bryn Mawr, Pennsylvania, 19010, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Einstein Healthcare Network
Philadelphia, Pennsylvania, 19141, United States
Cardiology consultants of Philadelphia
Yardley, Pennsylvania, 19067, United States
Baptist Hospital of Southeast Texas - Beaumont
Beaumont, Texas, 77701, United States
Southeast Texas Cardiology Associates II, L.L.P.
Beaumont, Texas, 77702, United States
Southeast Texas Cardiology Associates II, L.L.P
Beaumont, Texas, 77702, United States
Southeast Texas Clinical Research Center
Beaumont, Texas, 77702, United States
Utah Cardiology, PC
Layton, Utah, 84041, United States
Cardiovascular Associates of Virginia-Bon Secours St. Mary's Hospital
Midlothian, Virginia, 23114, United States
St. Francis Medical Center
Midlothian, Virginia, 23114, United States
Dominion Cardiovascular Specialists PLLC
Richmond, Virginia, 23225, United States
Sint-Franciskusziekenhuis
Heusden-Zolder, Limburg, 3550, Belgium
University Hospital Ghent
Ghent, Oost-vlaanderen, 9000, Belgium
UZ Leuven
Leuven, Vlaams Brabant, 3000, Belgium
Algemeen Ziekenhuis Klina
Brasschaat, 2930, Belgium
Grand Hopital de Charleroi asbl
Gilly, 6060, Belgium
Jessa Ziekenhuis-Campus Virga Jesse
Hasselt, 3500, Belgium
AZ Delta
Roeselare, 8800, Belgium
Cliniques Universitatires UCL Mont-Godinne
Yvoir, 5530, Belgium
Southlake Regional Health Centre
Newmarket, Ontario, L3Y 2P9, Canada
Institut de Cardiologie de Montreal -ICM / Montreal Heart Institute-MHI
Montreal, Quebec, H1T 1C8, Canada
McGill University Health Center
Montreal, Quebec, H3G 1A4, Canada
Regionshospitalet Silkeborg
Silkeborg, Central Jutland, DK-8600, Denmark
Slagelse Hospital
Slagelse, Region Sjælland, DK-4200, Denmark
Sydvestjysk Sygehus Esbjerg
Esbjerg, 6700, Denmark
Regionhospitalet Viborg
Viborg, DK-8800, Denmark
Cardio Centrum Ludwigsburg Bietigheim
Ludwigsburg, Baden-Wurttemberg, 71634, Germany
Charitè Campus Mitte/ Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie
Berlin, 10117, Germany
Vivantes -Netzwerk fuer Gesundheit GmbH - Klinikum Neukoelln
Berlin, 12351, Germany
Charité - Campus Virchow-Klinikum
Berlin, 13353, Germany
Vivantes Netzwerk fuer Gesundhelt GmbH, Humboldt Klinikum
Berlin, 13509, Germany
Klinikum Links der Weser gGmbH
Bremen, 28277, Germany
Medizinisches Versorgungszentrum am Küchwald GmbH
Chemnitz, 09113, Germany
Klinikum Coburg gGmbH
Coburg, 96450, Germany
Zentrum fuer klinische Pruefungen in der Facharztzentrum Dresden-Neustadt GbR
Dresden, 01099, Germany
Praxisklinik Herz und Gefäße
Dresden, 01324, Germany
Johanniter-Krankenhaus Rheinhausen GmbH/ Klinik fuer Kardiologie
Duisburg, 47228, Germany
Krankenhaus Nordwest GmbH
Frankfurt am Main, 60488, Germany
Johann-Wolfgang Goethe-Universitaet
Frankfurt am Main, 60590, Germany
Universitatsmedizin Greifswald
Greifswald, 17475, Germany
Universitätsklinikum Hamburg Eppendorf, Universitäres Herzzentrum Hamburg GmbH
Hamburg, 20246, Germany
Unklinik Heidelberg
Heidelberg, 69120, Germany
Klinikum Heidenheim
Heidenheim, 89522, Germany
Klinikum Ingolstadt/ Medizinische Klinik I und IV
Ingolstadt, 85049, Germany
Cardiocenter Rhythmologie
Leipzig, 04289, Germany
Herzzentrum Leipzig GmbH/ Abteilung für Rhythmologie
Leipzig, 04289, Germany
Katholisches Klinikum Mainz
Mainz, 55131, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, 55131, Germany
Kliniken Maria Hilf GmbH
Mönchengladbach, 41063, Germany
Universitaetsklinikum Tuebingen
Tübingen, 72076, Germany
Prof. Dr. med. Werner Jung,Schwarzwald - Baar Klinikum
Villingen-Schwenningen, 78052, Germany
Josephs-Hospital Warendorf
Warendorf, 48231, Germany
HaEmek Medical Center
Afula, 18101, Israel
Barzilai Medical Center (Cardiology)
Ashkelon, 78278, Israel
Soroka University Medical Centre, Soroka Medical center
Beersheba, 84101, Israel
Hillel Yaffe Medical Center
Hadera, 38100, Israel
Rambam Health Care Campus
Haifa, 31096, Israel
Lady Davis Carmel Medical Center
Haifa, 34362, Israel
Shaare Zedek Medical Center
Jerusalem, 91031, Israel
Hadassah University Hospital - Mount Scopus
Jerusalem, 91240, Israel
Galilee Medical Center
Nahariya, 22100, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Kaplan Medical Center
Rehovot, 76100, Israel
ZIV Medical Center
Safed, 13100, Israel
Clinical Trial Network Services
Tel Aviv, 64239, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
The Baruch Padeh Medical Center
Tiberias, 1528001, Israel
Ospedale Generale Regionale F. Miulli-Ente Ecclesiastico
Acquaviva Delle Fonti (BA), BARI, 70021, Italy
Policlinico Universitario Campus Biomedico
Rome, Lazio, 00128, Italy
I.R.C.C.S. Ospedale San Raffaele S.r.l.
Milan, Lombardy, 20132, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
Torrette Di Ancona, The Marches, 60020, Italy
Presidio Ospedaliero San Donato
Arezzo, 52100, Italy
Azienda Ospedaliero Universitaria Careggi, Medicina e Cardiologia Geriatrica
Florence, 50134, Italy
Centro Cardiologico Monzino
Milan, 20138, Italy
DAI Malattie Cardiovascolari e Respiratorie
Roma, 00161, Italy
Tosei General Hospital
Seto, Aichi-ken, 489-8642, Japan
Toho University Ohashi Medical Center
Meguro-ku, Tokyo, 153-8515, Japan
Osaka General Medical Center
Osaka, 558-8558, Japan
Nippon Medical School Hospital
Tokyo, 113-8603, Japan
Brasov Emergency Clinical County Hospital
Brasov, 500326, Romania
"Prof. Dr.C.C. lliescu" Emergency Institute for Cardiovascular Diseases Bucharest
Bucharest, 022328, Romania
Bucharest Emergency University Hospital
Bucharest, 050098, Romania
Cluj-Napoca Rehabilitation Clinical Hospital
Cluj-Napoca, 400347, Romania
Craiova Emergency Clinical County Hospital
Craiova, 200642, Romania
Prof.Dr.George I.M. Georgescu Cardiovascular Diseases Institute
Iași, 700503, Romania
Cardio Med SRL
Târgu Mureş, 540124, Romania
Tirgu Mures Emergency Clinical County Hospital
Târgu Mureş, 540139, Romania
Korea University Guro Hospital
Seoul, Korea, Republic of, 152-703, South Korea
Dong-A Unversity Hospital
Busan, 49201, South Korea
Keimyung University Dongsan Medical Center
Daegu, 700-712, South Korea
Yeungnam University Hospital
Deagu, 705703, South Korea
Chonnam National University Hospital
Gwangju, 501-757, South Korea
Seoul National University Hospital
Seoul, 110-744, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 120752, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
Korea University Anam Hospital, cardiology and Electrophysiology
Seoul, 136-705, South Korea
The Catholic University of Korea Seoul ST.MARY'S Hospital
Seoul, 137701, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Ajou University Hospital, Division of Cardiology
Suwon, 443-380, South Korea
Hospital Universitario San Juan de Alicante
San Juan, Alicante, 03550, Spain
Hospital de Sierrallana
Torrelavega, Cantabria, 39300, Spain
Consorci Sanitari de Terrassa Hospital de Terrassa
Terrassa, Catalonia, 08227, Spain
Hospital Universitario Infanta Sofía
San Sebastián de los Reyes, Madrid, 28702, Spain
Hospital de Basurto
Bilbao, 48013, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28007, Spain
Fundacion Jimenez Diaz
Madrid, 28040, Spain
Danderyds Sjukhus AB
Stockholm, Södermanland County, Sweden
Akademiska Sjukhuset I Uppsala/ Kardiologikliniken
Uppsala, Uppsala IAN, Sweden
Sahlgrenska University Hospital
Gothenburg, 41345, Sweden
Linkopings Universitetssjukhus Kardiologkliniken
Linköping, 581 85, Sweden
Universitetssjukhuset i Orebro/ Hjartmottagningen
Örebro, 701 85, Sweden
Skelleftea Country Hospital
Skellefteå, 931 86, Sweden
Sodersjukhuset
Stockholm, 11883, Sweden
Related Publications (1)
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.
PMID: 29659797DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The prioritization of outcome measures is not mentioned in the study documents (Statistical Analysis Plan and Protocol). The prioritization of outcome measures is based on team's discretion.
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2014
First Posted
March 31, 2014
Study Start
July 14, 2014
Primary Completion
February 8, 2017
Study Completion
February 8, 2017
Last Updated
May 23, 2018
Results First Posted
April 10, 2018
Record last verified: 2018-05