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)

Atrial Fibrillation Clinical Trial

— EMANATE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02100228
• Other study ID #: B0661025
• Secondary ID: CV185-2672014-00
• Status: Completed
• Phase: Phase 4
• Start date: July 14, 2014
• Est. completion date: February 8, 2017

Study information

• Verified date: May 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: February 8, 2017
• Est. primary completion date: February 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Apixaban
Oral, 2.5 or 5 mg BID
• Parenteral heparin and/or oral Vitamin K antagonist
Parenteral heparin and/or locally used oral Vitamin K antagonist e.g. warfarin (excludes other novel oral anticoagulants)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Romania,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Time to First Attempt of Cardioversion	Cardioversion was an effective method of converting an abnormally fast heart rate (tachycardia) or other cardiac arrhythmia to normal rhythm using electricity or drugs. First attempt of cardioversion was defined as the first time the participant was admitted for the cardioversion procedure.	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Secondary	Number of Participants With Different Type of Cardioversion Events	Cardioversion was an effective method of converting an abnormally fast heart rate (tachycardia) or other cardiac arrhythmia to normal rhythm using different type of cardioversion events i.e. electrical and pharmacologic. Electrical cardioversion was a procedure in which an electric current was used to reset the heart's rhythm back to its regular pattern (normal sinus rhythm). Pharmacologic cardioversion, also called chemical cardioversion, used antiarrhythmia medication instead of an electrical shock.	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Secondary	Number of Cardioversion Attempt of Participants	Cardioversion attempts were defined as the number of times the participant was admitted to hospital for the cardioversion procedure and not the number of attempts during a single hospital admission.	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Secondary	Number of Participants With Their Rhythm Status	Rhythm status was further distinguished into sinus rhythm, atrial fibrillation and atrial flutter. Sinus rhythm was defined as a normal heartbeat. Atrial fibrillation was an irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications and atrial flutter was a common abnormal heart rhythm that was usually associated with a fast heart rate (100 or more heart beats per minute).	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Secondary	Duration of Hospital Stay of Participants	Duration of hospital stay was defined as the number of hours from hospital admission to hospital discharge followed by early cardioversion.	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)
Secondary	Number of Participants Who Used Image Guidance Approach	An image-guided approach helped cardioversion earlier than the conventional minimum of 3 weeks of anticoagulation that would normally be required prior to cardioversion. Transesophageal echocardiography (TEE or TOE) and computed tomography (CT) were 2 image-guided approaches that were used in this study.	Baseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

External Links

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