MedPath

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)

Phase 4
Completed
Conditions
Atrial Fibrillation
Interventions
Drug: Parenteral heparin and/or oral Vitamin K antagonist
Registration Number
NCT02100228
Lead Sponsor
Pfizer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1500
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Parenteral heparin and/or oral Vitamin K antagonistParenteral heparin and/or oral Vitamin K antagonistParenteral heparin and/or locally used oral Vitamin K antagonist e.g. warfarin (excludes other novel oral anticoagulants)
ApixabanApixaban-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Acute Stroke EventBaseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)

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).

Number of Participants With Systemic Embolism EventBaseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)

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.

Number of Participants With Major Bleeding EventBaseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)

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.

Number of Participants With Clinically Relevant Non-Major Bleeding EventsBaseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)

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.

Number of Participants With All Cause DeathBaseline up to 30 days post cardioversion (or up to 90 days after randomization, if cardioversion was not performed within that time frame)
Secondary Outcome Measures
NameTimeMethod
Time to First Attempt of CardioversionBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

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.

Number of Participants With Different Type of Cardioversion EventsBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

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.

Number of Cardioversion Attempt of ParticipantsBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

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.

Number of Participants With Their Rhythm StatusBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

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).

Duration of Hospital Stay of ParticipantsBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

Duration of hospital stay was defined as the number of hours from hospital admission to hospital discharge followed by early cardioversion.

Number of Participants Who Used Image Guidance ApproachBaseline up to Day of first attempt of cardioversion procedure (Visit 2, up to 130 days)

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.

Trial Locations

Locations (164)

Policlinico Universitario Campus Biomedico

🇮🇹

Roma, Lazio, Italy

Brasov Emergency Clinical County Hospital

🇷🇴

Brasov, Romania

Prof.Dr.George I.M. Georgescu Cardiovascular Diseases Institute

🇷🇴

Iasi, Romania

Hospital Universitario San Juan de Alicante

🇪🇸

San Juan, Alicante, Spain

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

"Prof. Dr.C.C. lliescu" Emergency Institute for Cardiovascular Diseases Bucharest

🇷🇴

Bucharest, Romania

Cardio Med SRL

🇷🇴

Targu Mures, Romania

Tirgu Mures Emergency Clinical County Hospital

🇷🇴

Tirgu Mures, Romania

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

Hartford Hospital

🇺🇸

Hartford, Connecticut, United States

Aim Clinic

🇺🇸

Louisville, Kentucky, United States

New York-Presbyterian/Queens

🇺🇸

Flushing, New York, United States

UK Good Samaritan Medical Office Building

🇺🇸

Lexington, Kentucky, United States

Chicago Medical Research, LLC

🇺🇸

Hazel Crest, Illinois, United States

Oklahoma Heart Institute

🇺🇸

Tulsa, Oklahoma, United States

ProMedica Toledo Hospital

🇺🇸

Toledo, Ohio, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Integrated Medical Services, Inc./IMS Cardiology

🇺🇸

Avondale, Arizona, United States

University of Kentucky Medical Center Gill Heart Institute

🇺🇸

Lexington, Kentucky, United States

University of Missouri Health Care System

🇺🇸

Columbia, Missouri, United States

Charité - Campus Virchow-Klinikum

🇩🇪

Berlin, Germany

The University of Chicago Medical Center Investigational Drug Service Pharmacy

🇺🇸

Chicago, Illinois, United States

Brookwood Medical Center

🇺🇸

Birmingham, Alabama, United States

Good Samaritan Hospital

🇺🇸

Lexington, Kentucky, United States

State University of New York (SUNY) Downstate Medical Center

🇺🇸

Brooklyn, New York, United States

University of Louisville Hospital

🇺🇸

Louisville, Kentucky, United States

University of Massachusetts Worcester

🇺🇸

Worcester, Massachusetts, United States

Columbia University Medical Center/NY Presbyterian Hospital

🇺🇸

New York, New York, United States

University of Missouri Health System

🇺🇸

Columbia, Missouri, United States

Cliniques Universitatires UCL Mont-Godinne

🇧🇪

Yvoir, Belgium

Einstein Healthcare Network

🇺🇸

Philadelphia, Pennsylvania, United States

Minneapolis Heart Institute Foundation

🇺🇸

Minneapolis, Minnesota, United States

St. Francis Medical Center

🇺🇸

Midlothian, Virginia, United States

ProMedica Physicians Cardiology

🇺🇸

Toledo, Ohio, United States

Charitè Campus Mitte/ Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie

🇩🇪

Berlin, Germany

Sint-Franciskusziekenhuis

🇧🇪

Heusden-Zolder, Limburg, Belgium

AZ Delta

🇧🇪

Roeselare, Belgium

Institut de Cardiologie de Montreal -ICM / Montreal Heart Institute-MHI

🇨🇦

Montreal, Quebec, Canada

McGill University Health Center

🇨🇦

Montreal, Quebec, Canada

Cardiology Consultants of Philadelphia

🇺🇸

Bristol, Pennsylvania, United States

Rutgers Robert Wood Johnson Medical School Cardiovascular Institute

🇺🇸

New Brunswick, New Jersey, United States

Hillcrest Medical Center Pharmacy

🇺🇸

Tulsa, Oklahoma, United States

Oklahoma Heart Institute at Hillcrest Medical Center

🇺🇸

Tulsa, Oklahoma, United States

Jessa Ziekenhuis-Campus Virga Jesse

🇧🇪

Hasselt, Belgium

University of Cincinnati Medical Center

🇺🇸

Cincinnati, Ohio, United States

Southeast Texas Cardiology Associates II, L.L.P.

🇺🇸

Beaumont, Texas, United States

Zentrum fuer klinische Pruefungen in der Facharztzentrum Dresden-Neustadt GbR

🇩🇪

Dresden, Germany

Cardio Centrum Ludwigsburg Bietigheim

🇩🇪

Ludwigsburg, Baden-württemberg, Germany

Centro Cardiologico Monzino

🇮🇹

Milano, Italy

Keimyung University Dongsan Medical Center

🇰🇷

Daegu-si, Korea, Republic of

Medizinisches Versorgungszentrum am Küchwald GmbH

🇩🇪

Chemnitz, Germany

Unklinik Heidelberg

🇩🇪

Heidelberg, Germany

Hadassah University Hospital - Mount Scopus

🇮🇱

Jerusalem, Israel

Sydvestjysk Sygehus Esbjerg

🇩🇰

Esbjerg, Denmark

Clinical Trial Network Services

🇮🇱

Tel Aviv, Israel

Praxisklinik Herz und Gefäße

🇩🇪

Dresden, Germany

Universitätsklinikum Hamburg Eppendorf, Universitäres Herzzentrum Hamburg GmbH

🇩🇪

Hamburg, Germany

Slagelse Hospital

🇩🇰

Slagelse, Sjaelland, Denmark

Southlake Regional Health Centre

🇨🇦

Newmarket, Ontario, Canada

Johanniter-Krankenhaus Rheinhausen GmbH/ Klinik fuer Kardiologie

🇩🇪

Duisburg, Germany

Vivantes Netzwerk fuer Gesundhelt GmbH, Humboldt Klinikum

🇩🇪

Berlin, Germany

Klinikum Heidenheim

🇩🇪

Heidenheim, Germany

Yeungnam University Hospital

🇰🇷

Deagu, Korea, Republic of

Southeast Texas Cardiology Associates II, L.L.P

🇺🇸

Beaumont, Texas, United States

UZ Leuven

🇧🇪

Leuven, Vlaams Brabant, Belgium

Vivantes -Netzwerk fuer Gesundheit GmbH - Klinikum Neukoelln

🇩🇪

Berlin, Germany

Regionshospitalet Silkeborg

🇩🇰

Silkeborg, Midtjylland, Denmark

Hillel Yaffe Medical Center

🇮🇱

Hadera, Israel

Tosei General Hospital

🇯🇵

Seto, Aichi, Japan

Craiova Emergency Clinical County Hospital

🇷🇴

Craiova, Romania

Ajou University Hospital, Division of Cardiology

🇰🇷

Suwon, Korea, Republic of

Rambam Health Care Campus

🇮🇱

Haifa, Israel

Hospital de Basurto

🇪🇸

Bilbao, Spain

Cardiocenter Rhythmologie

🇩🇪

Leipzig, Germany

HaEmek Medical Center

🇮🇱

Afula, Israel

Lady Davis Carmel Medical Center

🇮🇱

Haifa, Israel

Sahlgrenska University Hospital

🇸🇪

Göteborg, Sweden

Johann-Wolfgang Goethe-Universitaet

🇩🇪

Frankfurt/Main, Germany

Korea University Anam Hospital, cardiology and Electrophysiology

🇰🇷

Seoul, Korea, Republic of

Azienda Ospedaliero Universitaria Careggi, Medicina e Cardiologia Geriatrica

🇮🇹

Firenze, Italy

Kaplan Medical Center

🇮🇱

Rehovot, Israel

Presidio Ospedaliero San Donato

🇮🇹

Arezzo, Italy

Krankenhaus Nordwest GmbH

🇩🇪

Frankfurt am Main, Germany

Hospital Universitario Infanta Sofía

🇪🇸

San Sebastián De Los Reyes, Madrid, Spain

DAI Malattie Cardiovascolari e Respiratorie

🇮🇹

Roma, Italy

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Universitatsmedizin Greifswald

🇩🇪

Greifswald, Germany

The Baruch Padeh Medical Center

🇮🇱

Tiberias, Israel

Osaka General Medical Center

🇯🇵

Osaka, Japan

Galilee Medical Center

🇮🇱

Nahariya, Israel

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Dong-A Unversity Hospital

🇰🇷

Busan, Korea, Republic of

Katholisches Klinikum Mainz

🇩🇪

Mainz, Germany

Prof. Dr. med. Werner Jung,Schwarzwald - Baar Klinikum

🇩🇪

Villingen-Schwenningen, Germany

Nippon Medical School Hospital

🇯🇵

Tokyo, Japan

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

I.R.C.C.S. Ospedale San Raffaele S.r.l.

🇮🇹

Milano, Lombardia, Italy

ZIV Medical Center

🇮🇱

Safed, Israel

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Rabin Medical Center

🇮🇱

Petach Tikva, Israel

The Catholic University of Korea Seoul ST.MARY'S Hospital

🇰🇷

Seoul, Korea, Republic of

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Consorci Sanitari de Terrassa Hospital de Terrassa

🇪🇸

Terrassa, Cataluna, Spain

Skelleftea Country Hospital

🇸🇪

Skelleftea, Sweden

Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Linkopings Universitetssjukhus Kardiologkliniken

🇸🇪

Linkoping, Sweden

Universitetssjukhuset i Orebro/ Hjartmottagningen

🇸🇪

Orebro, Sweden

Franciscan Physician Network-Indiana Heart Physicians

🇺🇸

Indianapolis, Indiana, United States

Franciscan St. Francis Health

🇺🇸

Indianapolis, Indiana, United States

Regionhospitalet Viborg

🇩🇰

Viborg, Denmark

Josephs-Hospital Warendorf

🇩🇪

Warendorf, Germany

Cardiovascular Associates of the Southeast, LLC

🇺🇸

Birmingham, Alabama, United States

Chula Vista Cardiac Center

🇺🇸

Chula Vista, California, United States

Certified Physician Investigator Research Group LLC

🇺🇸

Altamonte Springs, Florida, United States

Orlando Heart Specialists

🇺🇸

Altamonte Springs, Florida, United States

University of Kentucky HealthCare/Albert. B, Chandler Hospital

🇺🇸

Lexington, Kentucky, United States

University of Kentucky Gill Heart Institute

🇺🇸

Lexington, Kentucky, United States

University of Massachusetts Worcester Research Pharmacy

🇺🇸

Worcester, Massachusetts, United States

Abbott Northwestern Hopsital - Allina Health System

🇺🇸

Minneapolis, Minnesota, United States

William Beaumont Hospital

🇺🇸

Royal Oak, Michigan, United States

University of Missouri Health System, Investigational Drug Serivce

🇺🇸

Columbia, Missouri, United States

Saint Luke's Lipid and Diabetes Research Center

🇺🇸

Kansas City, Missouri, United States

Mercy Hospital St. Louis

🇺🇸

Saint Louis, Missouri, United States

Robert Wood Johnson University Hospital

🇺🇸

New Brunswick, New Jersey, United States

Pennsylvania Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Bryn Mawr Medical Specialist Association

🇺🇸

Bryn Mawr, Pennsylvania, United States

Penn State Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Baptist Hospital of Southeast Texas - Beaumont

🇺🇸

Beaumont, Texas, United States

Utah Cardiology, PC

🇺🇸

Layton, Utah, United States

Cardiology consultants of Philadelphia

🇺🇸

Yardley, Pennsylvania, United States

Cardiovascular Associates of Virginia-Bon Secours St. Mary's Hospital

🇺🇸

Midlothian, Virginia, United States

Southeast Texas Clinical Research Center

🇺🇸

Beaumont, Texas, United States

University Hospital Ghent

🇧🇪

Gent, Oost-vlaanderen, Belgium

Dominion Cardiovascular Specialists PLLC

🇺🇸

Richmond, Virginia, United States

Algemeen Ziekenhuis Klina

🇧🇪

Brasschaat, Belgium

Grand Hopital de Charleroi asbl

🇧🇪

Gilly, Belgium

Klinikum Links der Weser gGmbH

🇩🇪

Bremen, Germany

Klinikum Coburg gGmbH

🇩🇪

Coburg, Germany

Klinikum Ingolstadt/ Medizinische Klinik I und IV

🇩🇪

Ingolstadt, Germany

Herzzentrum Leipzig GmbH/ Abteilung für Rhythmologie

🇩🇪

Leipzig, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

🇩🇪

Mainz, Germany

Kliniken Maria Hilf GmbH

🇩🇪

Moenchengladbach, Germany

Barzilai Medical Center (Cardiology)

🇮🇱

Ashkelon, Israel

Soroka University Medical Centre, Soroka Medical center

🇮🇱

Be'er Sheva, Israel

Ospedale Generale Regionale F. Miulli-Ente Ecclesiastico

🇮🇹

Acquaviva Delle Fonti (BA), Bari, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

🇮🇹

Torrette Di Ancona, Marche, Italy

Toho University Ohashi Medical Center

🇯🇵

Meguro-ku, Tokyo, Japan

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Korea University Guro Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Bucharest Emergency University Hospital

🇷🇴

Bucharest, Romania

Cluj-Napoca Rehabilitation Clinical Hospital

🇷🇴

Cluj-Napoca, Romania

Hospital de Sierrallana

🇪🇸

Torrelavega, Cantabria, Spain

Danderyds Sjukhus AB

🇸🇪

Stockholm, Sodermanlands LAN, Sweden

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Akademiska Sjukhuset I Uppsala/ Kardiologikliniken

🇸🇪

Uppsala, Uppsala IAN, Sweden

Sodersjukhuset

🇸🇪

Stockholm, Sweden

University of Louisville Clinical Trials Unit

🇺🇸

Louisville, Kentucky, United States

Electrophysiology Associates

🇺🇸

Hackensack, New Jersey, United States

Cardiology Outpatient Clinic

🇺🇸

Louisville, Kentucky, United States

Robley Rex VA Medical Center

🇺🇸

Louisville, Kentucky, United States

Alexandria Cardiology Clinic

🇺🇸

Alexandria, Louisiana, United States

Bryn Mawr Hospital

🇺🇸

Bryn Mawr, Pennsylvania, United States

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