A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention

NCT ID: NCT01830543

Last Updated: 2017-09-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-10

Study Completion Date

2016-07-28

Brief Summary

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The primary purpose of this study is to evaluate the safety for 2 different rivaroxaban treatment strategies and one Vitamin K Antagonist (VKA) treatment strategy utilizing various combinations of dual antiplatelet therapy (DAPT) or low-dose aspirin (ASA) or clopidogrel (or prasugrel or ticagrelor).

Detailed Description

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This is an open-label (both physician and participant know the treatment that the participant receives), randomized (study medication is assigned by chance), multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and one vitamin K antagonist (VKA) treatment strategy in participants, who have paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and have had a percutaneous coronary intervention (PCI) with stent placement.

A target of 2,100 participants will be randomized into the study, with approximately 700 participants in each treatment strategy group. The randomization will be stratified by the intended duration of DAPT (1, 6, or 12 months).

The study consists of a screening phase, a 12-month open-label treatment phase, and an end-of-treatment/early withdrawal visit. The total duration of participation in the study for each participant is approximately 12 months.

Conditions

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Atrial Fibrillation Percutaneous Coronary Intervention

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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rivaroxaban 2.5 mg twice daily

rivaroxaban 2.5 mg tablet twice daily plus low-dose aspirin (ASA) 75 to 100 mg once daily and clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by rivaroxaban 15 mg tablet (or 10 mg for subjects with moderate renal impairment) once daily plus low-dose ASA for 12 months

Group Type EXPERIMENTAL

rivaroxaban 2.5 mg

Intervention Type DRUG

One 2.5 mg tablet twice daily for up to twelve months

rivaroxaban 15 mg

Intervention Type DRUG

One 15 mg tablet once daily for up to twelve months

rivaroxaban 10 mg

Intervention Type DRUG

One 10 mg tablet once daily for up to twelve months

aspirin (ASA)

Intervention Type DRUG

Low-dose aspirin tablet once daily for twelve months

clopidogrel

Intervention Type DRUG

One 75 mg tablet once daily for up to twelve months

prasugrel

Intervention Type DRUG

One 10 mg tablet once daily for up to twelve months

ticagrelor

Intervention Type DRUG

One 90 mg tablet twice daily for up to twelve months

vitamin K antagonist (VKA)

dose-adjusted vitamin K antagonist (VKA) once daily (target International Normalized Ratio (INR) 2.0 to 3.0) plus low-dose ASA, 75 to 100 mg per day, and clopidogrel 75 mg once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by dose-adjusted VKA once daily (target INR 2.0 to 3.0 or 2.0 to 2.5 at the investigator discretion) plus low-dose ASA for 12 months

Group Type EXPERIMENTAL

aspirin (ASA)

Intervention Type DRUG

Low-dose aspirin tablet once daily for twelve months

vitamin K antagonist (VKA)

Intervention Type DRUG

Dose-adjusted VKA tablet (target International Normalized Ratio (INR) 2.0 to 3.0) once daily for twelve months

clopidogrel

Intervention Type DRUG

One 75 mg tablet once daily for up to twelve months

prasugrel

Intervention Type DRUG

One 10 mg tablet once daily for up to twelve months

ticagrelor

Intervention Type DRUG

One 90 mg tablet twice daily for up to twelve months

rivaroxaban 15 mg once daily

rivaroxaban 15 mg (or 10 mg for subjects with moderate renal impairment) once daily plus clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) for 12 months

Group Type EXPERIMENTAL

rivaroxaban 15 mg

Intervention Type DRUG

One 15 mg tablet once daily for up to twelve months

rivaroxaban 10 mg

Intervention Type DRUG

One 10 mg tablet once daily for up to twelve months

clopidogrel

Intervention Type DRUG

One 75 mg tablet once daily for up to twelve months

prasugrel

Intervention Type DRUG

One 10 mg tablet once daily for up to twelve months

ticagrelor

Intervention Type DRUG

One 90 mg tablet twice daily for up to twelve months

Interventions

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rivaroxaban 2.5 mg

One 2.5 mg tablet twice daily for up to twelve months

Intervention Type DRUG

rivaroxaban 15 mg

One 15 mg tablet once daily for up to twelve months

Intervention Type DRUG

rivaroxaban 10 mg

One 10 mg tablet once daily for up to twelve months

Intervention Type DRUG

aspirin (ASA)

Low-dose aspirin tablet once daily for twelve months

Intervention Type DRUG

vitamin K antagonist (VKA)

Dose-adjusted VKA tablet (target International Normalized Ratio (INR) 2.0 to 3.0) once daily for twelve months

Intervention Type DRUG

clopidogrel

One 75 mg tablet once daily for up to twelve months

Intervention Type DRUG

prasugrel

One 10 mg tablet once daily for up to twelve months

Intervention Type DRUG

ticagrelor

One 90 mg tablet twice daily for up to twelve months

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Have a documented medical history of paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF)
* Have undergone percutaneous coronary intervention (PCI) procedure (with stent placement) for primary atherosclerotic disease
* Must have an international normalized ratio (INR) of 2.5 or below to be randomized
* Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active
* Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol

Exclusion Criteria

* Have any condition that contraindicates anticoagulant or antiplatelet therapy or would have an unacceptable risk of bleeding, such as, but not limited to: platelet count \<90,000/microliter at screening, history of intracranial hemorrhage, 12 month history of clinically significant gastrointestinal bleeding, non-VKA induced elevated prothrombin time (PT) at screening
* Have anemia of unknown cause with a hemoglobin level \<10 g/dL (\<6.21 mmol/L)
* Have a history of stroke or Transient Ischemic Attack (TIA)
* Have a calculated Creatinine Clearance (CrCl) \<30 mL/min at screening
* Have known significant liver disease or liver function test (LFT) abnormalities
* Have any severe condition that would limit life expectancy to less than 12 months
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

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Huntsville, Alabama, United States

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Los Alamitos, California, United States

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Mission Viejo, California, United States

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Oceanside, California, United States

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Riverside, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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Stockton, California, United States

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Thousand Oaks, California, United States

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Torrance, California, United States

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Colorado Springs, Colorado, United States

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Lakewood, Colorado, United States

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Littleton, Colorado, United States

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Danbury, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Atlantis, Florida, United States

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Clearwater, Florida, United States

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Daytona Beach, Florida, United States

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Jacksonville, Florida, United States

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Port Charlotte, Florida, United States

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Safety Harbor, Florida, United States

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St. Petersburg, Florida, United States

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Tallahassee, Florida, United States

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Tampa, Florida, United States

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Columbus, Georgia, United States

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Macon, Georgia, United States

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Marietta, Georgia, United States

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Boise, Idaho, United States

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Hazel Crest, Illinois, United States

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Indianapolis, Indiana, United States

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Munster, Indiana, United States

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Hammond, Louisiana, United States

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Lake Charles, Louisiana, United States

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Slidell, Louisiana, United States

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Auburn, Maine, United States

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Bangor, Maine, United States

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Baltimore, Maryland, United States

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Detroit, Michigan, United States

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Lansing, Michigan, United States

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Mount Clemens, Michigan, United States

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Petoskey, Michigan, United States

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Ypsilanti, Michigan, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Kalispell, Montana, United States

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Las Vegas, Nevada, United States

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Hackensack, New Jersey, United States

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Haddon Heights, New Jersey, United States

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New Brunswick, New Jersey, United States

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Newark, New Jersey, United States

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Ridgewood, New Jersey, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

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Peekskill, New York, United States

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Sanford, North Carolina, United States

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Bartlesville, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Bend, Oregon, United States

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Portland, Oregon, United States

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Abington, Pennsylvania, United States

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Camp Hill, Pennsylvania, United States

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Doylestown, Pennsylvania, United States

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Erie, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Sayre, Pennsylvania, United States

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York, Pennsylvania, United States

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Greenville, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Jackson, Tennessee, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Fort Worth, Texas, United States

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Humble, Texas, United States

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Odessa, Texas, United States

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Plano, Texas, United States

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Layton, Utah, United States

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Charlottesville, Virginia, United States

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Manassas, Virginia, United States

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Midlothian, Virginia, United States

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Richmond, Virginia, United States

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Bellevue, Washington, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Weston, Wisconsin, United States

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Bahía Blanca, , Argentina

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Buenos Aires, , Argentina

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C.a.b.a., , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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La Plata, , Argentina

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Resistencia, , Argentina

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Rosario, , Argentina

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Santa Fe, , Argentina

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Vicente López, , Argentina

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Chermside, , Australia

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Epping, , Australia

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Hobart, , Australia

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Kogarah, , Australia

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Liverpool, , Australia

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New Lambton, , Australia

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Wollongong, , Australia

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Aalst, , Belgium

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Bonheiden, , Belgium

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Brasschaat, , Belgium

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Bruges, , Belgium

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Brussels, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Liège, , Belgium

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Mechelen, , Belgium

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Mol, , Belgium

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Roeselare, , Belgium

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Turnhout, , Belgium

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Belo Horizonte, , Brazil

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Blumenau, , Brazil

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Brasília, , Brazil

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Campina Grande do Sul, , Brazil

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Campinas, , Brazil

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Curitiba, , Brazil

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Marília, , Brazil

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Passo Fundo, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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Uberlândia, , Brazil

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Votuporanga, , Brazil

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Blagoevgrad, , Bulgaria

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Burgas, , Bulgaria

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Edmonton, Alberta, Canada

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Maple Ridge, British Columbia, Canada

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New Westminster, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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St. John's, Newfoundland and Labrador, Canada

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Greater Sudbury, Ontario, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Chicoutimi, , Canada

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Saint John, , Canada

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Alto, , Chile

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Concepción, , Chile

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Punta Arenas, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Brno, , Czechia

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Hradec Králové, , Czechia

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Jablonec Na Nisou, , Czechia

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Karlovy Vary, , Czechia

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Kladno, , Czechia

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Litomyšl, , Czechia

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Olomouc, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Praha 10 N/A, , Czechia

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Slaný, , Czechia

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Uherské Hradiště, , Czechia

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Aalborg, , Denmark

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Copenhagen, , Denmark

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Esbjerg, , Denmark

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Herlev, , Denmark

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Herning, , Denmark

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Hvidovre, , Denmark

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Koege, , Denmark

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Næstved, , Denmark

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Odense, , Denmark

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Roskilde, , Denmark

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Svendborg, , Denmark

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Vejle, , Denmark

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Besancon Cedex Franche-Comté, , France

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Caen, , France

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Centrès, , France

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Chartres, , France

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Lille, , France

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Limoges, , France

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Marseille, , France

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Montfermeil, , France

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Nantes, , France

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Nîmes, , France

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Paris, , France

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Pau, , France

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Pessac, , France

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Poitiers, , France

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Toulouse, , France

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Bad Friedrichshall, , Germany

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Bad Nauheim, , Germany

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Berlin, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Esslingen am Neckar, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Göttingen, , Germany

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Greifswald, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Limburg, , Germany

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Mannheim, , Germany

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Ulm, , Germany

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Witten, , Germany

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George Town, , Malaysia

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Johor Bahru, , Malaysia

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Kajang, , Malaysia

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Kuala Lumpur, , Malaysia

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Aguascalientes, , Mexico

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Guadalajara, , Mexico

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León, , Mexico

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México, , Mexico

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Pachuca, , Mexico

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Puebla City, , Mexico

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Querétaro, , Mexico

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Villahermosa, , Mexico

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Zapopan, , Mexico

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's-Hertogenbosch, , Netherlands

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Alkmaar, , Netherlands

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Amsterdam, , Netherlands

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Amsterdam-Zuidoost, , Netherlands

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Breda, , Netherlands

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Delft, , Netherlands

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Gorinchem, , Netherlands

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Leiden, , Netherlands

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Maastricht, , Netherlands

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Nieuwegein, , Netherlands

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Sneek, , Netherlands

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Uden, , Netherlands

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Będzin, , Poland

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Bielsko-Biala, , Poland

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Chrzanów, , Poland

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Gdynia, , Poland

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Grodzisk Mazowiecki, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Mielec, , Poland

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Nowy Targ, , Poland

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Ostrowiec Świętokrzyski, , Poland

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Oświęcim, , Poland

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Płock, , Poland

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Rzeszow Poland, , Poland

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Starachowice, , Poland

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Starogard Gdański, , Poland

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Szczecin, , Poland

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Torun, , Poland

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Tychy, , Poland

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Ustroń, , Poland

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Warsaw, , Poland

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Zamość, , Poland

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Târgu Mureş, , Romania

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Tg Mures, , Romania

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Arkhangelsk, , Russia

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Barnaul, , Russia

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Chita, , Russia

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Kemerovo, , Russia

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Krasnodar, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Perm, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Syktyvkar, , Russia

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Tyumen, , Russia

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Yekaterinburg, , Russia

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Cape Town, , South Africa

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Centurion, , South Africa

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Linksfield West, Johannesburg, , South Africa

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Somerset West, , South Africa

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Busan, , South Korea

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Daejeon, , South Korea

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Gyeonggi-do, , South Korea

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Incheon, , South Korea

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Seongnam, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Uijeongbu-si, , South Korea

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Wŏnju, , South Korea

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Falun, , Sweden

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Gothenburg, , Sweden

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Jönköping, , Sweden

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Lund, , Sweden

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Malmo, , Sweden

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Örebro, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul Nap, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Sivas, , Turkey (Türkiye)

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Cherkassy, , Ukraine

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Khemelnitskiy, , Ukraine

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Kyiv, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Rivne, , Ukraine

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Uzhhorod, , Ukraine

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Zaporizhzhya, , Ukraine

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Bath, , United Kingdom

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Birmingham, , United Kingdom

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Blackburn, , United Kingdom

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Bradford, , United Kingdom

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Clydebank, , United Kingdom

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Cottingham, , United Kingdom

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Coventry, , United Kingdom

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Dorchester, , United Kingdom

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Dundee, , United Kingdom

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Edinburgh, , United Kingdom

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Exeter, , United Kingdom

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Hampshire, , United Kingdom

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Harrow, , United Kingdom

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High Wycombe, , United Kingdom

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London, , United Kingdom

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Middlesbrough, , United Kingdom

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Norwich, , United Kingdom

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Nottingham, , United Kingdom

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Plymouth, , United Kingdom

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Portsmouth, , United Kingdom

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Torquay, , United Kingdom

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Truro, , United Kingdom

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Worcester, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Bulgaria Canada Chile Czechia Denmark France Germany Malaysia Mexico Netherlands Poland Romania Russia South Africa South Korea Sweden Taiwan Turkey (Türkiye) Ukraine United Kingdom

References

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Kerneis M, Yee MK, Mehran R, Nafee T, Bode C, Halperin JL, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Fox KAA, Gibson CM. Novel Oral Anticoagulant Based Versus Vitamin K Antagonist Based Double Therapy Among Stented Patients With Atrial Fibrillation: Insights From the PIONEER AF-PCI Trial. Circ Cardiovasc Interv. 2019 Nov;12(11):e008160. doi: 10.1161/CIRCINTERVENTIONS.119.008160. Epub 2019 Nov 11.

Reference Type DERIVED
PMID: 31707805 (View on PubMed)

Gibson WJ, Nafee T, Travis R, Yee M, Kerneis M, Ohman M, Gibson CM. Machine learning versus traditional risk stratification methods in acute coronary syndrome: a pooled randomized clinical trial analysis. J Thromb Thrombolysis. 2020 Jan;49(1):1-9. doi: 10.1007/s11239-019-01940-8.

Reference Type DERIVED
PMID: 31535314 (View on PubMed)

Kerneis M, Yee MK, Mehran R, Nafee T, Bode C, Halperin JL, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Fox KAA, Gibson CM. Association of International Normalized Ratio Stability and Bleeding Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2019 Feb;12(2):e007124. doi: 10.1161/CIRCINTERVENTIONS.118.007124.

Reference Type DERIVED
PMID: 30704287 (View on PubMed)

Chi G, Kerneis M, Kalayci A, Liu Y, Mehran R, Bode C, Halperin JL, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Peterson ED, Fox KAA, Gibson CM. Safety and efficacy of non-vitamin K oral anticoagulant for atrial fibrillation patients after percutaneous coronary intervention: A bivariate analysis of the PIONEER AF-PCI and RE-DUAL PCI trial. Am Heart J. 2018 Sep;203:17-24. doi: 10.1016/j.ahj.2018.06.003. Epub 2018 Jun 13.

Reference Type DERIVED
PMID: 30015064 (View on PubMed)

Chi G, Yee MK, Kalayci A, Kerneis M, AlKhalfan F, Mehran R, Bode C, Halperin JL, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Cohen M, Peterson ED, Fox KAA, Gibson CM. Total bleeding with rivaroxaban versus warfarin in patients with atrial fibrillation receiving antiplatelet therapy after percutaneous coronary intervention. J Thromb Thrombolysis. 2018 Oct;46(3):346-350. doi: 10.1007/s11239-018-1703-5.

Reference Type DERIVED
PMID: 29943350 (View on PubMed)

Kerneis M, Gibson CM, Chi G, Mehran R, AlKhalfan F, Talib U, Pahlavani S, Mir M, Bode C, Halperin JL, Nafee T, Peterson ED, Verheugt FWA, Wildgoose P, van Eickels M, Lip GYH, Fox KAA, Cohen M. Effect of Procedure and Coronary Lesion Characteristics on Clinical Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the PIONEER AF-PCI Trial. JACC Cardiovasc Interv. 2018 Apr 9;11(7):626-634. doi: 10.1016/j.jcin.2017.11.009. Epub 2018 Mar 14.

Reference Type DERIVED
PMID: 29550085 (View on PubMed)

Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016 Dec 22;375(25):2423-2434. doi: 10.1056/NEJMoa1611594. Epub 2016 Nov 14.

Reference Type DERIVED
PMID: 27959713 (View on PubMed)

Gibson CM, Pinto DS, Chi G, Arbetter D, Yee M, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Burton P, van Eickels M, Korjian S, Daaboul Y, Jain P, Lip GY, Cohen M, Peterson ED, Fox KA. Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy. Circulation. 2017 Jan 24;135(4):323-333. doi: 10.1161/CIRCULATIONAHA.116.025783. Epub 2016 Nov 14.

Reference Type DERIVED
PMID: 27881555 (View on PubMed)

Gibson CM, Mehran R, Bode C, Halperin J, Verheugt F, Wildgoose P, van Eickels M, Lip GY, Cohen M, Husted S, Peterson E, Fox K. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Am Heart J. 2015 Apr;169(4):472-8.e5. doi: 10.1016/j.ahj.2014.12.006. Epub 2014 Dec 20.

Reference Type DERIVED
PMID: 25819853 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RIVAROXAFL3003

Identifier Type: OTHER

Identifier Source: secondary_id

2012-001491-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100758

Identifier Type: -

Identifier Source: org_study_id