Study Stopped
Study halted early due to no efficacy improvement over aspirin at an interim analysis and very little chance of showing overall benefit if study were completed
Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source (ESUS)
NAVIGATE ESUS
Multicenter, Randomized, Double-blind, Double-dummy, Active-comparator, Event-driven, Superiority Phase III Study of Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With a Recent Embolic Stroke of Undetermined Source (ESUS), Comparing Rivaroxaban 15 mg Once Daily With Aspirin 100 mg
2 other identifiers
interventional
7,213
30 countries
444
Brief Summary
This is a study in patients who recently had a brain attack (stroke) and in whom no clear cause of the stroke could be identified. These strokes are likely due to a blood clot and therefore, can be called embolic stroke of undetermined source. The abbreviation is ESUS. The study will compare 2 blood thinners. Patients will be randomly assigned to either Rivaroxaban 15 mg or Aspirin 100 mg and the study is intended to show, if patients given rivaroxaban have fewer blood clots in the brain (stroke) or in other blood vessels.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 stroke
Started Dec 2014
444 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 8, 2014
CompletedFirst Posted
Study publicly available on registry
December 10, 2014
CompletedStudy Start
First participant enrolled
December 23, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 15, 2018
CompletedResults Posted
Study results publicly available
January 9, 2019
CompletedJanuary 9, 2019
December 1, 2018
3.2 years
December 8, 2014
November 20, 2018
December 20, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence Rate of the Composite Efficacy Outcome (Adjudicated)
Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)
Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (\>=) 2 grams per decilitre (g/dL) (20 grams per liter \[g/L\]; 1.24 millimoles per liter \[mmol/L\]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
From randomization until the efficacy cut-off date (median 326 days)
Secondary Outcomes (6)
Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction
From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of All-Cause Mortality
From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction
From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Life-Threatening Bleeding Events
From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Clinically Relevant Non-Major Bleeding Events
From randomization until the efficacy cut-off date (median 326 days)
- +1 more secondary outcomes
Study Arms (2)
Rivaroxaban
EXPERIMENTALRivaroxaban 15 mg orally once daily
Aspirin
ACTIVE COMPARATORAspirin 100 mg orally once daily
Interventions
Eligibility Criteria
You may qualify if:
- Recent ESUS (between 7 days and 6 months), defined as:
- Recent ischemic stroke (including transient ischemic attack with positive neuroimaging) visualized by brain imaging that is not lacunar, and
- Absence of cervical carotid atherosclerotic stenosis\> 50% or occlusion, and
- No atrial fibrillation after ≥ 24-hour cardiac rhythm monitoring, and
- No intra-cardiac thrombus on either transesophageal or transthoracic echocardiography, and
- No other specific cause of stroke (for example, arteritis, dissection, migraine/vasospasm, drug abuse)
You may not qualify if:
- Severely disabling stroke (modified Rankin score ≥4)
- Indication for chronic anticoagulation or antiplatelet therapy
- Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\^2
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- Janssen Research & Development, LLCcollaborator
- Population Health Research Institutecollaborator
Study Sites (454)
Unknown Facility
Tucson, Arizona, 85724, United States
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Long Beach, California, 90806, United States
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Stanford, California, 94305-5119, United States
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Torrance, California, 90502, United States
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New Haven, Connecticut, 06520-8064, United States
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Gainesville, Florida, 32611, United States
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Joliet, Illinois, 60435, United States
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Iowa City, Iowa, 52242-1089, United States
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Lexington, Kentucky, 40536, United States
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New Orleans, Louisiana, 70121, United States
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Baltimore, Maryland, 21210, United States
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Boston, Massachusetts, 02111, United States
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Boston, Massachusetts, 02118, United States
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Worcester, Massachusetts, 01655, United States
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Ann Arbor, Michigan, 48109-0330, United States
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Mount Clemens, Michigan, 48043, United States
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New Brunswick, New Jersey, 08901, United States
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Buffalo, New York, 14203, United States
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New York, New York, 10016-4576, United States
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Cincinnati, Ohio, 45219, United States
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Cleveland, Ohio, 44106-2602, United States
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Cleveland, Ohio, 44195, United States
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Portland, Oregon, 97225, United States
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Portland, Oregon, 97239-3011, United States
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Erie, Pennsylvania, 16550, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Charleston, South Carolina, 29425, United States
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Columbia, South Carolina, 29203-8004, United States
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Nashville, Tennessee, 37232-5400, United States
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Austin, Texas, 78701, United States
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Dallas, Texas, 75390, United States
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El Paso, Texas, 79905-2709, United States
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Houston, Texas, 77030, United States
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San Antonio, Texas, 78229, United States
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Temple, Texas, 76504, United States
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Salt Lake City, Utah, 84312, United States
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Seattle, Washington, 98102, United States
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Banfield, Buenos Aires, 1828, Argentina
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Ciudad Auton. de Buenos Aires, Buenos Aires, C1405CNF, Argentina
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Mar del Plata, Buenos Aires, B7602CBM, Argentina
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San Martín, Buenos Aires, 1650, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, 1078, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, 1428, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, C1039AAO, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, C1221 ADC, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, C1431FWO, Argentina
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Buenos Aires, Ciudad Auton. de Buenos Aires, C1437JCP, Argentina
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Rosario, Santa Fe Province, S2000DSV, Argentina
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Rosario, Santa Fe Province, Argentina
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Ciudad Auton. de Buenos Aires, C1425DND, Argentina
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Córdoba, X5000JHQ, Argentina
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Santa Fe, 3000, Argentina
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Camperdown, New South Wales, 2050, Australia
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Waratah, New South Wales, 2298, Australia
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Brisbane, Queensland, 4029, Australia
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Southport, Queensland, 4215, Australia
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Launceston, Tasmania, 7250, Australia
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Clayton, Victoria, 3168, Australia
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Footscray, Victoria, 3011, Australia
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Murdoch, Western Australia, 6150, Australia
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Elizabeth Vale, 5112, Australia
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Nedlands, 6009, Australia
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Klagenfurt, Carinthia, 9020, Austria
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Villach, Carinthia, 9500, Austria
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Bad Pirawarth, Lower Austria, 2222, Austria
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Sankt Pölten, Lower Austria, 3100, Austria
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Feldbach, Styria, 8330, Austria
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Vöcklabruck, Upper Austria, 4840, Austria
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Feldkirch, Vorarlberg, 6807, Austria
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Salzburg, 5020, Austria
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Vienna, 1020, Austria
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Vienna, 1090, Austria
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Bruges, West-Vlaanderen, 8310, Belgium
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Antwerp, 2020, Belgium
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Brussels, 1090, Belgium
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Bruxelles - Brussel, 1070, Belgium
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Dendermonde, 9200, Belgium
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Edegem, 2650, Belgium
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Hasselt, 3500, Belgium
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Salvador, Estado de Bahia, 41253-190, Brazil
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Belo Horizonte, Minas Gerais, 30130-100, Brazil
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Belo Horizonte, Minas Gerais, 30150-221, Brazil
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Porto Alegre, Rio Grande do Sul, 90035-001, Brazil
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Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
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Porto Alegre, Rio Grande do Sul, Brazil
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Joinville, Santa Catarina, 89202-165, Brazil
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Botucatu, São Paulo, 18618 970, Brazil
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Campinas, São Paulo, 13081-000, Brazil
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Matão, São Paulo, 15990-060, Brazil
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Ribeirão Preto, São Paulo, 14015-130, Brazil
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Ribeirão Preto, São Paulo, 14048-900, Brazil
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São Paulo, São Paulo, 01228-000, Brazil
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São Paulo, São Paulo, 08270-070, Brazil
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Rio de Janeiro, 22281-100, Brazil
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Calgary, Alberta, T2N 2T9, Canada
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Edmonton, Alberta, T6G 2B7, Canada
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Edmonton, Alberta, T6L 5X8, Canada
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Lethbridge, Alberta, T1K 0C9, Canada
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Vancouver, British Columbia, V5Z 1M9, Canada
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Victoria, British Columbia, V8R 1J8, Canada
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Brandon, Manitoba, R7A 2B3, Canada
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Saint John, New Brunswick, E2L 4L2, Canada
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Halifax, Nova Scotia, B3H 2Y5, Canada
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Burlington, Ontario, L7M 4Y1, Canada
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Hamilton, Ontario, L8L 2X2, Canada
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Kingston, Ontario, K7L 2V7, Canada
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London, Ontario, N6A 5A5, Canada
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London, Ontario, N6G 2V4, Canada
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Mississauga, Ontario, L5B 2V2, Canada
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Ottawa, Ontario, K1Y 4E9, Canada
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Thunder Bay, Ontario, P7K 0A4, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Chicoutimi, Quebec, G7H 5H6, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Montreal, Quebec, H3G 1A4, Canada
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Saint-Jérôme, Quebec, J7Z 5T3, Canada
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Québec, G1J 1Z4, Canada
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Los Ángeles, Bío-Bío, Chile
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Osorno, Los Lagos Region, Chile
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Port Montt, Los Lagos Region, 5506667, Chile
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Valdivia, Los Lagos Region, Chile
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Viña del Mar, Región de Valparaíso, Chile
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Santiago, 7650567, Chile
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Santiago, 8420524, Chile
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Viña del Mar, Chile
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Fuzhou, Fujian, 350001, China
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Fuzhou, Fujian, 350005, China
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Lanzhou, Gansu, 730000, China
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Foshan, Guangdong, 528000, China
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Guangzhou, Guangdong, 510080, China
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Haikou, Hainan, 570311, China
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Shijiazhuang, Hebei, 050000, China
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Harbin, Heilongjiang, China
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Zhengzhou, Henan, 450052, China
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Wuhan, Hubei, 430014, China
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Wuhan, Hubei, 430034, China
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Wuhan, Hubei, 430060, China
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Changsha, Hunan, 410008, China
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Baotou, Inner Mongolia, 014010, China
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Nantong, Jiangsu, 226001, China
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Nanchang, Jiangxi, 330006, China
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Changchun, Jilin, 130021, China
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Shenyang, Liaoning, 110016, China
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Qingdao, Shandong, 266003, China
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Yantai, Shandong, 264000, China
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Baoji, Shanxi, 721008, China
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Xi’an, Shanxi, 710038, China
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Kunming, Yunnan, 650032, China
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Hangzhou, Zhejiang, 310009, China
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Taizhou, Zhejiang, 317000, China
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Wenzhou, Zhejiang, 325000, China
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Beijing, 100050, China
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Beijing, 100730, China
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Chongqing, China
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Guangzhou, China
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Shanghai, 200032, China
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Tianjin, 300000, China
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Tianjin, 300052, China
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Blansko, 67801, Czechia
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Brno, 625 00, Czechia
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Brno, 656 91, Czechia
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Hradec Králové, 500 05, Czechia
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Jihlava, 58633, Czechia
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Olomouc, 775 20, Czechia
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Ostrava Vitkovice, Czechia
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Ostrava-Poruba, 708 52, Czechia
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Prague, 10034, Czechia
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Prague, 128 21, Czechia
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Vyškov, 682 01, Czechia
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Aalborg, 9100, Denmark
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Aarhus C, 8000, Denmark
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Copenhagen, 2400, Denmark
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Glostrup Municipality, 2600, Denmark
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Herlev, 2730, Denmark
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Hillerød, 3400, Denmark
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Helsinki, 00029, Finland
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Lappeenranta, FIN-53130, Finland
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OYS, 90029, Finland
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Sairaalamäki, 45750, Finland
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Tampere, FIN-33520, Finland
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Turku, 20520, Finland
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Vaasa, 65130, Finland
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Antony, 92166, France
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Bordeaux, 33000, France
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Brest, 29609, France
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Caen, 14033, France
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Dijon, 21033, France
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Le Chesnay, 78150, France
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Limoges, 87042, France
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Nantes, 44035, France
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Nîmes, 30029, France
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Paris, 75012, France
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Paris, 75018, France
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Paris, 75475, France
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Paris, 75634, France
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Paris, 75674, France
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Saint-Priest-en-Jarez, 42270, France
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Strasbourg, 67091, France
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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany
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Mannheim, Baden-Wurttemberg, 68167, Germany
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München, Bavaria, 81675, Germany
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Regensburg, Bavaria, 93053, Germany
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Würzburg, Bavaria, 97080, Germany
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Hanover, Lower Saxony, 30625, Germany
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Düsseldorf, North Rhine-Westphalia, 40225, Germany
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Meerbusch, North Rhine-Westphalia, 40670, Germany
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Wuppertal, North Rhine-Westphalia, 42283, Germany
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Dresden, Saxony, 01129, Germany
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Dresden, Saxony, 01307, Germany
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Markkleeberg, Saxony, 04416, Germany
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Wermsdorf, Saxony, 04779, Germany
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Halle, Saxony-Anhalt, 06120, Germany
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Altenburg, Thuringia, 04600, Germany
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Berlin, 12200, Germany
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Hamburg, 22417, Germany
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Athens, 11521, Greece
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Athens, 11528, Greece
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Ioannina, 45500, Greece
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Larissa, 41100, Greece
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Thessaloniki, 546 36, Greece
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Budapest, 1083, Hungary
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Budapest, 1134, Hungary
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Budapest, 1204, Hungary
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Debrecen, 4012, Hungary
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Eger, 3300, Hungary
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Győr, 9002, Hungary
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Kistarcsa, 2143, Hungary
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Miskolc, 35-26, Hungary
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Nagykanizsa, 8800, Hungary
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Nyíregyháza, H-4400, Hungary
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Sopron, 9400, Hungary
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Szeged, 6720, Hungary
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Zalaegerszeg, 8900, Hungary
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Dublin, DUBLIN 7, Ireland
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Galway, Ireland
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Ashkelon, 7827804, Israel
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Beersheba, 8410101, Israel
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Haifa, 3339419, Israel
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Haifa, 3436212, Israel
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Jerusalem, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 5262000, Israel
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Tel Aviv, 6423906, Israel
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L’Aquila, Abruzzo, 67100, Italy
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Vibo Valentia, Calabria, 89900, Italy
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Parma, Emilia-Romagna, 43126, Italy
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Trieste, Friuli Venezia Giulia, 34100, Italy
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Rome, Lazio, 00133, Italy
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Rome, Lazio, 00152, Italy
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Rome, Lazio, 00161, Italy
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Rome, Lazio, 00168, Italy
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Milan, Lombardy, 20122, Italy
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Milan, Lombardy, 20132, Italy
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Milan, Lombardy, 20162, Italy
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Pavia, Lombardy, 27100, Italy
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Isernia, Molise, 86077, Italy
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Cagliari, Sardinia, 09134, Italy
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Ancona, The Marches, 60126, Italy
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Perugia, Umbria, 06012, Italy
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Perugia, Umbria, 06024, Italy
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Perugia, Umbria, 06156, Italy
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Verona, Veneto, 37024, Italy
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Verona, Veneto, 37126, Italy
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Nagoya, Aichi-ken, 454-8502, Japan
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Nagoya, Aichi-ken, 457-8511, Japan
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Nagoya, Aichi-ken, 460-0001, Japan
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Okazaki, Aichi-ken, 444-8553, Japan
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Seto, Aichi-ken, 489-8642, Japan
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Toyota, Aichi-ken, 471-8513, Japan
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Kitakyushu, Fukuoka, 802-8555, Japan
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Kitakyushu, Fukuoka, 805-0050, Japan
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Kōriyama, Fukushima, 963-8052, Japan
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Fukuyama, Hiroshima, 720-0825, Japan
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Asahikawa, Hokkaido, 070-8530, Japan
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Hakodate, Hokkaido, 041-0802, Japan
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Kushiro, Hokkaido, 085-0061, Japan
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Kobe, Hyōgo, 650-0047, Japan
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Kobe, Hyōgo, 652-0803, Japan
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Kobe, Hyōgo, 654-0048, Japan
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Nishinomiya, Hyōgo, 663-8211, Japan
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Isehara, Kanagawa, 259-1193, Japan
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Kawasaki, Kanagawa, 216-8511, Japan
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Sendai, Miyagi, 982-8523, Japan
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Sasebo, Nagasaki, 857-0134, Japan
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Tenri, Nara, 632-8552, Japan
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Kurashiki, Okayama-ken, 710-8602, Japan
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Matsubara, Osaka, 580-0032, Japan
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Sakai, Osaka, 590-0064, Japan
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Suita, Osaka, 565-8565, Japan
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Hidaka, Saitama, 350-1298, Japan
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Bunkyo-ku, Tokyo, 113-8603, Japan
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Hachiōji, Tokyo, 192-0032, Japan
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Kodaira, Tokyo, 187-8510, Japan
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Musashino, Tokyo, 180-8610, Japan
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Shinjuku-ku, Tokyo, 162-8666, Japan
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Sumida-ku, Tokyo, 130-8575, Japan
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Fukuoka, 810-0001, Japan
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Fukuoka, 810-8563, Japan
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Fukuoka, 811-0213, Japan
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Hiroshima, 730-8518, Japan
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Kakogawa, 675-0122, Japan
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Kochi, 780-8522, Japan
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Kyoto, 600-8558, Japan
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Kyoto, 601-1495, Japan
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Kyoto, 602-8026, Japan
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Niigata, 950-1197, Japan
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Okayama, 700-8557, Japan
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Gustavo Adolfo Madero, Mexico City, 07760, Mexico
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México, D.F., Mexico City, 14080, Mexico
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Morelia, Michoacán, 58000, Mexico
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México D.F., México, 06720, Mexico
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Monterrey, Nuevo León, 64460, Mexico
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Mérida, Yucatán, 97070, Mexico
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Aguascalientes, 20127, Mexico
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México D.F., Mexico
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Bialystok, 15-276, Poland
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Chełm, 22-100, Poland
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Gdansk, 80-803, Poland
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Gdansk, 80-952, Poland
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Gmina Końskie, 26-200, Poland
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Katowice, 40-635, Poland
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Lodz, 90-153, Poland
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Lodz, 90-549, Poland
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Olsztyn, 10-561, Poland
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Sandomierz, Poland
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Siedlce, 08-110, Poland
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Skarżysko-Kamienna, 26-110, Poland
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Warsaw, 00-146, Poland
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Warsaw, 02957, Poland
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Warsaw, 03-242, Poland
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Vilanova de Gaia, Porto District, 4434-502, Portugal
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Almada, 2801-951, Portugal
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Amadora, 2720-276, Portugal
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Coimbra, 3030-075, Portugal
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Lisbon, 1198, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-319, Portugal
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Vila Franca de Xira, P 2600-178, Portugal
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Chelyabinsk, 454021, Russia
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Kaluga, 248010, Russia
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Kazan', 420012, Russia
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Krasnoyarsk, 660022, Russia
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Moscow, 117997, Russia
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Moscow, 119049, Russia
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Nizhny Novgorod, 603005, Russia
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Saint Petersburg, 190068, Russia
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Saint Petersburg, 191186, Russia
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Saint Petersburg, 194354, Russia
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Saint Petersburg, 196247, Russia
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Tomsk, 634063, Russia
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Ulyanovsk, 432063, Russia
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Volgograd, 400131, Russia
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Yaroslavl, 150000, Russia
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Yekaterinburg, 620017, Russia
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Yekaterinburg, 620102, Russia
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Cape Town, Western Cape, 7531, South Africa
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Somerset West, Western Cape, 7130, South Africa
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Durban, 4100, South Africa
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Donggu, Gwangju Gwang''yeogsi, 61469, South Korea
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Anyang-si, Gyeonggido, 431-070, South Korea
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Goyang, Gyeonggido, 411-706, South Korea
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Seongnam-si, Gyeonggido, 463-707, South Korea
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Seoul, Seoul Teugbyeolsi, 152-703, South Korea
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Busan, 49201, South Korea
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Daegu, 41931, South Korea
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Daegu, 42415, South Korea
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Incheon, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Seoul, 110-744, South Korea
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Seoul, 120-752, South Korea
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Seoul, 130-872, South Korea
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Seoul, 139-872, South Korea
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Santiago de Compostela, A Coruña, 15706, Spain
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Badalona, Barcelona, 08916, Spain
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Unknown Facility
Sant Joan Despí, Barcelona, 08970, Spain
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Castellon, Castellón, 12004, Spain
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El Palmar (Murcia), Murcia, 30120, Spain
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A Coruña, 15006, Spain
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Badajoz, 06080, Spain
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Barcelona, 08003, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Barcelona, 08041, Spain
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Bilbao, 48013, Spain
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Cáceres, 10003, Spain
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Girona, 17007, Spain
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Granada, 18014, Spain
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León, 24008, Spain
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Lleida, 25198, Spain
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Madrid, 28006, Spain
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Madrid, 28007, Spain
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Madrid, 28046, Spain
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Seville, 41009, Spain
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Seville, 41013, Spain
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Valencia, 46026, Spain
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Valladolid, 47011, Spain
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Zaragoza, 50009, Spain
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Gothenburg, 413 45, Sweden
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Hässleholm, 281 25, Sweden
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Lund, 221 85, Sweden
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Malmo, 205 02, Sweden
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Umeå, 901 85, Sweden
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Aarau, Canton of Aargau, 5001, Switzerland
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Basel, Canton of Basel-City, 4056, Switzerland
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Lugano, Canton Ticino, 6900, Switzerland
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Baden, 5404, Switzerland
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Bern, 3010, Switzerland
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Fribourg, 1700, Switzerland
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Geneva, 1205, Switzerland
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Zurich, 8032, Switzerland
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Ankara, 06500, Turkey (Türkiye)
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Ankara, 6100, Turkey (Türkiye)
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Antakya, 31000, Turkey (Türkiye)
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Istanbul, 34098, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Kahramanmaraş, 46000, Turkey (Türkiye)
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Konya, 42075, Turkey (Türkiye)
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Konya, 42080, Turkey (Türkiye)
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High Wycombe, Buckinghamshire, HP11 2TT, United Kingdom
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Milton Keynes, Buckinghamshire, MK6 5LD, United Kingdom
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Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
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Exeter, Devon, EX2 5DW, United Kingdom
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Colchester, Essex, CO4 5JR, United Kingdom
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Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom
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Gloucester, Gloucestershire, GL1 3NN, United Kingdom
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Watford, Hertfordshire, WD1 8HB, United Kingdom
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Ashford, Kent, TN24 0LZ, United Kingdom
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Margate, Kent, CT9 4AN, United Kingdom
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Leicester, Leicestershire, LE2 7LX, United Kingdom
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Boston, Lincolnshire, PE21 9QS, United Kingdom
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Harrow, London, HA1 3UJ, United Kingdom
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Great Yarmouth, Norfolk, NR31 6LA, United Kingdom
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Taunton, Somerset, TA1 5DA, United Kingdom
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Yeovil, Somerset, BA21 4AT, United Kingdom
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Sheffield, South Yorkshire, S10 2JF, United Kingdom
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Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
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Glasgow, Stratchclyde, G51 4TF, United Kingdom
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Gateshead, Tyne and Wear, NE9 6SX, United Kingdom
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Sunderland, Tyne and Wear, SR4 7TP, United Kingdom
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Wolverhampton, West Midlands, WV10 0QP, United Kingdom
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Leeds, West Yorkshire, LS1 3EX, United Kingdom
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Salisbury, Wiltshire, SP2 8BJ, United Kingdom
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Aberdeen, AB25 2ZN, United Kingdom
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Durham, DH1 5TW, United Kingdom
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Edinburgh, EH16 4SA, United Kingdom
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London, N18 1QX, United Kingdom
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London, SE5 8AF, United Kingdom
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London, W6 8RP, United Kingdom
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London, WC1N 3BG, United Kingdom
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Luton, LU4 0DZ, United Kingdom
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Norwich, NR4 7UY, United Kingdom
Related Publications (15)
Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, Swaminathan B, Lavados P, Wang Y, Wang Y, Davalos A, Shamalov N, Mikulik R, Cunha L, Lindgren A, Arauz A, Lang W, Czlonkowska A, Eckstein J, Gagliardi RJ, Amarenco P, Ameriso SF, Tatlisumak T, Veltkamp R, Hankey GJ, Toni D, Bereczki D, Uchiyama S, Ntaios G, Yoon BW, Brouns R, Endres M, Muir KW, Bornstein N, Ozturk S, O'Donnell MJ, De Vries Basson MM, Pare G, Pater C, Kirsch B, Sheridan P, Peters G, Weitz JI, Peacock WF, Shoamanesh A, Benavente OR, Joyner C, Themeles E, Connolly SJ; NAVIGATE ESUS Investigators. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. N Engl J Med. 2018 Jun 7;378(23):2191-2201. doi: 10.1056/NEJMoa1802686. Epub 2018 May 16.
PMID: 29766772RESULTKasner SE, Lavados P, Sharma M, Wang Y, Wang Y, Davalos A, Shamalov N, Cunha L, Lindgren A, Mikulik R, Arauz A, Lang W, Czlonkowska A, Eckstein J, Gagliardi R, Amarenco P, Ameriso SF, Tatlisumak T, Veltkamp R, Hankey GJ, Toni DS, Bereczki D, Uchiyama S, Ntaios G, Yoon BW, Brouns R, DeVries Basson MM, Endres M, Muir K, Bornstein N, Ozturk S, O'Donnell M, Mundl H, Pater C, Weitz J, Peacock WF, Swaminathan B, Kirsch B, Berkowitz SD, Peters G, Pare G, Themeles E, Shoamanesh A, Connolly SJ, Hart RG; NAVIGATE ESUS Steering Committee and Investigators. Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial. J Stroke Cerebrovasc Dis. 2018 Jun;27(6):1673-1682. doi: 10.1016/j.jstrokecerebrovasdis.2018.01.027. Epub 2018 Mar 7.
PMID: 29525076RESULTHart RG, Sharma M, Mundl H, Shoamanesh A, Kasner SE, Berkowitz SD, Pare G, Kirsch B, Pogue J, Pater C, Peters G, Davalos A, Lang W, Wang Y, Wang Y, Cunha L, Eckstein J, Tatlisumak T, Shamalov N, Mikulik R, Lavados P, Hankey GJ, Czlonkowska A, Toni D, Ameriso SF, Gagliardi RJ, Amarenco P, Bereczki D, Uchiyama S, Lindgren A, Endres M, Brouns R, Yoon BW, Ntaios G, Veltkamp R, Muir KW, Ozturk S, Arauz A, Bornstein N, Bryer A, O'Donnell MJ, Weitz J, Peacock F, Themeles E, Connolly SJ. Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: Design of the NAVIGATE ESUS randomized trial. Eur Stroke J. 2016 Sep;1(3):146-154. doi: 10.1177/2396987316663049. Epub 2016 Aug 3.
PMID: 31008276RESULTLee SF, Whiteley W, Bosch J, Sherlock L, Cukierman-Yaffe T, O'Donnell M, Eikelboom JW, Gerstein HC, Bangdiwala SI, Muniz-Terrera G. Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches. Trials. 2024 Oct 2;25(1):644. doi: 10.1186/s13063-024-08482-2.
PMID: 39358761DERIVEDSharma M, Smith EE, Pearce LA, Perera KS, Kasner SE, Yoon BW, Ameriso SF, Puig J, Damgaard D, Fiebach JB, Muir KW, Veltkamp RC, Toni DS, Shamalov N, Gagliardi RJ, Mikulik R, Engelter ST, Bereczki D, O'Donnell MJ, Saad F, Shoamanesh A, Berkowitz SD, Mundl H, Hart RG; NAVIGATE ESUS MRI Substudy Investigators. Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy. Int J Stroke. 2022 Aug;17(7):799-805. doi: 10.1177/17474930211058012. Epub 2021 Nov 18.
PMID: 34791941DERIVEDMerkler AE, Pearce LA, Kasner SE, Shoamanesh A, Birnbaum LA, Kamel H, Sheth KN, Sharma R. Left Ventricular Dysfunction Among Patients With Embolic Stroke of Undetermined Source and the Effect of Rivaroxaban vs Aspirin: A Subgroup Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA Neurol. 2021 Dec 1;78(12):1454-1460. doi: 10.1001/jamaneurol.2021.3828.
PMID: 34694346DERIVEDSharma M, Smith EE, Pearce LA, Shoamanesh A, Perera KS, Coutts SB, Damgaard D, Ameriso SF, Rha JH, Modrau B, Yoon BW, Romano M, Messe SR, Barlinn J, Lambeck J, Saad F, Berkowitz SD, Mundl H, Connolly SJ, Hart RG; NAVIGATE ESUS MIND MRI Substudy Investigators. Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial. Stroke. 2022 Jan;53(1):45-52. doi: 10.1161/STROKEAHA.120.032976. Epub 2021 Sep 20.
PMID: 34538089DERIVEDShoamanesh A, Hart RG, Connolly SJ, Kasner SE, Smith EE, Marti-Fabregas J, Liu YY, Uchiyama S, Mikulik R, Veltkamp R, O'Donnell MJ, Ntaios G, Muir KW, Field TS, Santo GC, Olavarria V, Mundl H, Lutsep H, Berkowitz SD, Sharma M. Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA Neurol. 2021 Jan 1;78(1):11-20. doi: 10.1001/jamaneurol.2020.3836.
PMID: 33074284DERIVEDScheitz JF, Pare G, Pearce LA, Mundl H, Peacock WF, Czlonkowska A, Sharma M, Nolte CH, Shoamanesh A, Berkowitz SD, Krahn T, Endres M; NAVIGATE-ESUS Biomarker Working Group. High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source. Stroke. 2020 Aug;51(8):2386-2394. doi: 10.1161/STROKEAHA.120.029628. Epub 2020 Jul 9.
PMID: 32640945DERIVEDVeltkamp R, Pearce LA, Korompoki E, Sharma M, Kasner SE, Toni D, Ameriso SF, Mundl H, Tatlisumak T, Hankey GJ, Lindgren A, Berkowitz SD, Arauz A, Ozturk S, Muir KW, Chamorro A, Perera K, Shuaib A, Rudilosso S, Shoamanesh A, Connolly SJ, Hart RG. Characteristics of Recurrent Ischemic Stroke After Embolic Stroke of Undetermined Source: Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol. 2020 Oct 1;77(10):1233-1240. doi: 10.1001/jamaneurol.2020.1995.
PMID: 32628266DERIVEDMikulik R, Eckstein J, Pearce LA, Mundl H, Rudilosso S, Olavarria VV, Shoamanesh A, Chamorro A, Marti-Fabregas J, Veltkamp R, Ozturk S, Tatlisumak T, Peacock WF, Berkowitz SD, Connolly SJ, Hart RG. Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial. Stroke. 2020 Jul;51(7):2139-2147. doi: 10.1161/STROKEAHA.119.027995. Epub 2020 Jun 10.
PMID: 32517582DERIVEDNtaios G, Pearce LA, Veltkamp R, Sharma M, Kasner SE, Korompoki E, Milionis H, Mundl H, Berkowitz SD, Connolly SJ, Hart RG; NAVIGATE ESUS Investigators. Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial. Stroke. 2020 Jun;51(6):1797-1804. doi: 10.1161/STROKEAHA.119.028669. Epub 2020 Apr 16.
PMID: 32295509DERIVEDMartinez-Majander N, Ntaios G, Liu YY, Ylikotila P, Joensuu H, Saarinen J, Perera KS, Marti-Fabregas J, Chamorro A, Rudilosso S, Prats-Sanchez L, Berkowitz SD, Mundl H, Themeles E, Tiainen M, Demchuk A, Kasner SE, Hart RG, Tatlisumak T; NAVIGATE ESUS investigators. Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial. Eur J Neurol. 2020 May;27(5):841-848. doi: 10.1111/ene.14172. Epub 2020 Mar 11.
PMID: 32056346DERIVEDNtaios G, Pearce LA, Meseguer E, Endres M, Amarenco P, Ozturk S, Lang W, Bornstein NM, Molina CA, Pagola J, Mundl H, Berkowitz SD, Liu YY, Sen S, Connolly SJ, Hart RG. Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial. Stroke. 2019 Nov;50(11):3184-3190. doi: 10.1161/STROKEAHA.119.025813. Epub 2019 Sep 17.
PMID: 31526123DERIVEDNtaios G, Swaminathan B, Berkowitz SD, Gagliardi RJ, Lang W, Siegler JE, Lavados P, Mundl H, Bornstein N, Meseguer E, Amarenco P, Cucchiara B, Camps-Renom P, Makaritsis K, Korompoki E, Papavasileiou V, Marti-Fabregas J, Milionis H, Vemmos K, Connolly SJ, Hart RG; NAVIGATE ESUS Investigators. Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis. Stroke. 2019 Sep;50(9):2477-2485. doi: 10.1161/STROKEAHA.119.025168. Epub 2019 Aug 12.
PMID: 31401971DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Study terminated early due to no efficacy improvement over aspirin at the second interim analysis and very little chance of showing overall benefit if the study were completed.
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer
Study Officials
- STUDY DIRECTOR
Bayer Study Director
Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2014
First Posted
December 10, 2014
Study Start
December 23, 2014
Primary Completion
February 15, 2018
Study Completion
February 15, 2018
Last Updated
January 9, 2019
Results First Posted
January 9, 2019
Record last verified: 2018-12