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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00831441




Registration number
NCT00831441
Ethics application status
Date submitted
28/01/2009
Date registered
28/01/2009
Date last updated
18/12/2015

Titles & IDs
Public title
Phase III Acute Coronary Syndrome
Scientific title
Apixaban for Prevention of Acute Ischemic Events - 2 A Phase 3, Randomized, Double-Blind, Evaluation of the Safety and Efficacy of Apixaban In Subjects With a Recent Acute Coronary Syndrome
Secondary ID [1] 0 0
EUDRACT# 2008-008298-77
Secondary ID [2] 0 0
CV185-068
Universal Trial Number (UTN)
Trial acronym
APPRAISE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Coronary Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Cardiovascular 0 0 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Apixaban
Treatment: Drugs - Placebo

Active Comparator: Apixaban -

Placebo Comparator: Placebo -


Treatment: Drugs: Apixaban
Tablets, Oral, 5 mg, twice daily, until study end

Treatment: Drugs: Placebo
Tablets, Oral, 0 mg, twice daily, until study end

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants - Event rate was percent of participants with an event of cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Study was terminated early and last patient, last visit was in Year 2. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes (eg, cardiogenic shock, heart failure, arrhythmia/sudden death, cardiac rupture, ischemic stroke, pulmonary embolism, venous/arterial thrombotic events) and other sudden deaths for which an alternative cause was not identified. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Timepoint [1] 0 0
Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years
Primary outcome [2] 0 0
Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants - TIMI Major Bleed Criteria: Fatal bleeding, intracranial hemorrhage, and clinically overt bleeding with a hemoglobin (Hgb) drop of = 5 grams per deciliter (g/dL), or =15% absolute decrease in hematocrit. To account for transfusions, Hgb measurements were adjusted for transfusions. A transfusion of 1 unit of blood was assumed to result in an increase by 1 g/dL in Hgb or 3% in hematocrit. Event rate was percent of participants with an event of Major Bleed as per TIMI (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Treatment Period=events with onset from first dose to last dose plus 2 days.
Timepoint [2] 0 0
From first dose to first occurrence of event (TIMI major bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years
Secondary outcome [1] 0 0
Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants - Unstable Angina (UA) defined as worsening or recurrent severe or repetitive angina symptoms at rest lasting at least 10 minutes with at least 2 of the following: New and dynamic electrocardiogram (ECG) changes; angina symptoms leading to inpatient hospitalization; angina symptoms leading to an unplanned or urgent cardiac catheterization, with or without revascularization, that showed evidence of hemodynamically and clinically significant stenosis. Event rate was percent of participants with an event of unstable angina (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Timepoint [1] 0 0
Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 years
Secondary outcome [2] 0 0
Event Rate of Stroke During the Intended Treatment Period - Randomized Participants - Event rate was percent of participants with an event of stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause (ie, brain tumor). All strokes were classified as hemorrhagic (documentation on imaging (eg computed tomography scan or magnetic resonance imaging) of hemorrhage in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage), non-hemorrhagic/ischemic stroke, ischemic stroke with hemorrhagic conversion, or type unknown. Intended Treatment Period: the period that started on the day of randomization (Day 1) and ended at the efficacy cut-off date (notification of study termination).
Timepoint [2] 0 0
Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 years
Secondary outcome [3] 0 0
Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants - MI took into account whether the participant had a recent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Selected key criteria: Elevation of cardiac biomarkers (eg, Creatine Kinase MB fraction (CKMB), Troponin T, Troponin I) above the upper reference limit (URL) plus ischemic symptoms, ECG changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; Death of CV etiology with new ST-segment elevation or left bundle branch block (LBBB) or fresh intracoronary thrombus by angiography or at autopsy occurring before biomarkers could be obtained or before their appearance in the blood; Following a PCI, elevation of cardiac biomarkers more than 3*URL; Following CABG surgery, elevation of cardiac biomarkers more than 5*URL; New, significant (=0.04 s) Q waves in =2 contiguous leads; Pathologic findings of acute MI. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice.
Timepoint [3] 0 0
Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 years
Secondary outcome [4] 0 0
Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants - Stent thrombosis: Definite stent thrombosis considered to have occurred by either angiographic or pathological confirmation; Probable stent thrombosis considered to have occurred in the following cases: any unexplained death within the first 30 days after stent implantation; irrespective of the time after the procedure, any MI that was related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause; Possible stent thrombosis considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of study (in Year 2). Event rate was percent of participants with an event of stent thrombosis (number with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice of study termination.
Timepoint [4] 0 0
Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 years
Secondary outcome [5] 0 0
Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants - Event rate was percent of participants with an event of CV death, MI, unstable angina (UA), or ischemic stroke (number of participants with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Each type of event was counted once per participant, but participants could have been counted in multiple categories. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Timepoint [5] 0 0
Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 years
Secondary outcome [6] 0 0
Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants - Event rate was percent of participants with an event of CV death, fatal bleed, MI, or stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes; Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause; Fatal bleeding defined as bleeding that Adjudication Committee determined was the primary cause of death or contributed directly to death; MI took into account whether the participant had a recent PCI or CABG surgery. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Timepoint [6] 0 0
Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 years
Secondary outcome [7] 0 0
Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants - Cause of death was determined by the principal condition that caused the death, not the immediate mode of death.
CV death: included deaths due to CV causes. Non-CV death: included non-CV deaths caused primarily by a malignancy, infection, bleeding, trauma, non-CV system organ failure, or non-CV surgery. Unknown: included deaths that were not attributable to one of the above categories of CV death or to a non-CV cause. MI accounted whether the participant had a recent PCI or CABG surgery. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause. Only events confirmed by the adjudication committee were included in analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Timepoint [7] 0 0
Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 years
Secondary outcome [8] 0 0
Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants - ISTH Criteria: Acute clinically overt bleeding defined as new onset, visible bleeding or signs or symptoms suggestive of bleeding confirmed by imaging techniques, which can detect the presence of blood (eg, ultrasound, CT, MRI). Major bleeding: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed red blood cells (RBCs); Bleeding that occurs in at least one of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. Bleeding events were adjudicated by the Adjudication Committee. Event rate was percent of participants with an event (number with event/number randomized) per 100-pt years. Treatment Period=events with onset from first dose to last dose plus 2 days.
Timepoint [8] 0 0
From first dose to first occurrence of event (ISTH major bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years
Secondary outcome [9] 0 0
Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants - ISTH Major bleed: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed RBCs; Bleeding that occurs in at least one of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. CRNM: acute clinically overt bleeding that did not satisfy additional criteria required for the bleeding event to be defined as a major bleeding event and meets at least one of the following: Hospital admission for bleeding; Physician guided medical or surgical treatment for bleeding; Change in anti-thrombotic treatment (anticoagulant or antiplatelet) therapy. Bleeding events were adjudicated by the Adjudication Committee. Treatment Period=events with onset from first dose to last dose plus 2 days.
Timepoint [9] 0 0
From first dose to first occurrence of event (ISTH major or CRNM bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years
Secondary outcome [10] 0 0
Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants - Bleeding events were adjudicated by the Adjudication Committee and classified according to Thrombolysis in Myocardial Infarction (TIMI) major, minor, minimal, and International Society on Thrombosis and Hemostasis (ISTH) major and clinically relevant non-major bleeding (CRNM) criteria. The adjudicated results based on TIMI and ISTH classifications, and programmatically identified events (not adjudicated) according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification were used in the analyses of bleeding endpoints. GUSTO Bleed Criteria included Severe or life-threatening: Intracranial hemorrhage, or bleeding that causes hemodynamic compromise requiring intervention; Moderate: Bleeding that requires a blood transfusion, but does not result in hemodynamic compromise; Mild: Bleeding that does not meet criteria for either severe or moderate bleeding. Treatment Period=events with onset from first dose to last dose plus 2 days.
Timepoint [10] 0 0
From first dose to first occurrence of event (Bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years

Eligibility
Key inclusion criteria
- Acute coronary syndrome (ACS)

- Clinically stable

- Receiving standard of care for ACS
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Severe hypertension

- Active bleeding or high risk for major bleeding

- Hemoglobin < 9 g/dL

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Bruce
Recruitment hospital [2] 0 0
Local Institution - Broken Hill
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Local Institution - Kogarah
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Local Institution - Lismore
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Local Institution - Cairns
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Local Institution - Herston
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Local Institution - Milton
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Local Institution - Ashford
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Local Institution - Elizabeth Vale
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Local Institution - Woodville
Recruitment hospital [11] 0 0
Local Institution - Fitzroy
Recruitment hospital [12] 0 0
Local Institution - Geelong
Recruitment hospital [13] 0 0
Local Institution - Richmond
Recruitment postcode(s) [1] 0 0
2617 - Bruce
Recruitment postcode(s) [2] 0 0
2880 - Broken Hill
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2480 - Lismore
Recruitment postcode(s) [5] 0 0
4870 - Cairns
Recruitment postcode(s) [6] 0 0
4031 - Herston
Recruitment postcode(s) [7] 0 0
4064 - Milton
Recruitment postcode(s) [8] 0 0
5035 - Ashford
Recruitment postcode(s) [9] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [10] 0 0
5011 - Woodville
Recruitment postcode(s) [11] 0 0
3065 - Fitzroy
Recruitment postcode(s) [12] 0 0
3220 - Geelong
Recruitment postcode(s) [13] 0 0
3121 - Richmond
Recruitment outside Australia
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Chaco
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Hubei
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Hunan
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China
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Jiangsu
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China
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Jiangxi
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China
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Jilin
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China
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Liaoning
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China
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Shandong
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China
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Shanghai
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China
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Sichuan
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China
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Yunnan
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China
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Zhejiang
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China
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Xian
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Colombia
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Bolivar
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Country [130] 0 0
Colombia
State/province [130] 0 0
Floridablanca
Country [131] 0 0
Colombia
State/province [131] 0 0
Manizales
Country [132] 0 0
Colombia
State/province [132] 0 0
Medelin
Country [133] 0 0
Colombia
State/province [133] 0 0
Medellin
Country [134] 0 0
Czech Republic
State/province [134] 0 0
Brno
Country [135] 0 0
Czech Republic
State/province [135] 0 0
Hradec Kralove
Country [136] 0 0
Czech Republic
State/province [136] 0 0
Liberec
Country [137] 0 0
Czech Republic
State/province [137] 0 0
Novy Jicin
Country [138] 0 0
Czech Republic
State/province [138] 0 0
Olomouc
Country [139] 0 0
Czech Republic
State/province [139] 0 0
Ostrava
Country [140] 0 0
Czech Republic
State/province [140] 0 0
Praha 10
Country [141] 0 0
Czech Republic
State/province [141] 0 0
Rakovnik
Country [142] 0 0
Czech Republic
State/province [142] 0 0
Usti Nad Orlici
Country [143] 0 0
Denmark
State/province [143] 0 0
Arhus C
Country [144] 0 0
Denmark
State/province [144] 0 0
Copenhagen
Country [145] 0 0
Denmark
State/province [145] 0 0
Esbjerg
Country [146] 0 0
Denmark
State/province [146] 0 0
Haderslev
Country [147] 0 0
Denmark
State/province [147] 0 0
Hellerup
Country [148] 0 0
Denmark
State/province [148] 0 0
Hillerod
Country [149] 0 0
Denmark
State/province [149] 0 0
Hvidovre
Country [150] 0 0
Denmark
State/province [150] 0 0
Naestved
Country [151] 0 0
Denmark
State/province [151] 0 0
Silkeborg
Country [152] 0 0
Denmark
State/province [152] 0 0
Slagelse
Country [153] 0 0
Finland
State/province [153] 0 0
Espoo
Country [154] 0 0
Finland
State/province [154] 0 0
Helsinki
Country [155] 0 0
Finland
State/province [155] 0 0
Rovaniemi
Country [156] 0 0
Finland
State/province [156] 0 0
Tampere
Country [157] 0 0
France
State/province [157] 0 0
Albi Cedex 09
Country [158] 0 0
France
State/province [158] 0 0
Amiens Cedex 1
Country [159] 0 0
France
State/province [159] 0 0
Avignon
Country [160] 0 0
France
State/province [160] 0 0
Cholet
Country [161] 0 0
France
State/province [161] 0 0
Lagny Sur Marne
Country [162] 0 0
France
State/province [162] 0 0
Langres Cedex
Country [163] 0 0
France
State/province [163] 0 0
Montpellier
Country [164] 0 0
France
State/province [164] 0 0
Paris Cedex 13
Country [165] 0 0
France
State/province [165] 0 0
Pau Universite Cedex
Country [166] 0 0
France
State/province [166] 0 0
Strasbourg Cedex
Country [167] 0 0
France
State/province [167] 0 0
Toulouse Cedex 03
Country [168] 0 0
Germany
State/province [168] 0 0
Bad Berka
Country [169] 0 0
Germany
State/province [169] 0 0
Bad Nauheim
Country [170] 0 0
Germany
State/province [170] 0 0
Berlin
Country [171] 0 0
Germany
State/province [171] 0 0
Bernau
Country [172] 0 0
Germany
State/province [172] 0 0
Bonn
Country [173] 0 0
Germany
State/province [173] 0 0
Chemnitz
Country [174] 0 0
Germany
State/province [174] 0 0
Coswig
Country [175] 0 0
Germany
State/province [175] 0 0
Cottbus
Country [176] 0 0
Germany
State/province [176] 0 0
Dachau
Country [177] 0 0
Germany
State/province [177] 0 0
Essen
Country [178] 0 0
Germany
State/province [178] 0 0
Flensburg
Country [179] 0 0
Germany
State/province [179] 0 0
Halle/Saale
Country [180] 0 0
Germany
State/province [180] 0 0
Hamburg
Country [181] 0 0
Germany
State/province [181] 0 0
Hoyerswerda
Country [182] 0 0
Germany
State/province [182] 0 0
Jena
Country [183] 0 0
Germany
State/province [183] 0 0
Leverkusen
Country [184] 0 0
Germany
State/province [184] 0 0
Limburg
Country [185] 0 0
Germany
State/province [185] 0 0
Luebeck
Country [186] 0 0
Germany
State/province [186] 0 0
Mainz
Country [187] 0 0
Germany
State/province [187] 0 0
Muenster
Country [188] 0 0
Germany
State/province [188] 0 0
Neuss
Country [189] 0 0
Germany
State/province [189] 0 0
Paderborn
Country [190] 0 0
Germany
State/province [190] 0 0
Pirna
Country [191] 0 0
Germany
State/province [191] 0 0
Regensburg
Country [192] 0 0
Germany
State/province [192] 0 0
Rostock
Country [193] 0 0
Germany
State/province [193] 0 0
Wesel
Country [194] 0 0
Hungary
State/province [194] 0 0
Baja
Country [195] 0 0
Hungary
State/province [195] 0 0
Balatonfured
Country [196] 0 0
Hungary
State/province [196] 0 0
Budapest
Country [197] 0 0
Hungary
State/province [197] 0 0
Budpest
Country [198] 0 0
Hungary
State/province [198] 0 0
Cegled
Country [199] 0 0
Hungary
State/province [199] 0 0
Debrecen
Country [200] 0 0
Hungary
State/province [200] 0 0
Dunaujvaros
Country [201] 0 0
Hungary
State/province [201] 0 0
Hodmezovasarhely
Country [202] 0 0
Hungary
State/province [202] 0 0
Kecskemet
Country [203] 0 0
Hungary
State/province [203] 0 0
Miskolc
Country [204] 0 0
Hungary
State/province [204] 0 0
Szekesfehervar
Country [205] 0 0
Hungary
State/province [205] 0 0
Szekszard
Country [206] 0 0
Hungary
State/province [206] 0 0
Szentes
Country [207] 0 0
Hungary
State/province [207] 0 0
Szombathely
Country [208] 0 0
Hungary
State/province [208] 0 0
Zalaegerszeg
Country [209] 0 0
India
State/province [209] 0 0
Andhra Pradesh
Country [210] 0 0
India
State/province [210] 0 0
Gujarat
Country [211] 0 0
India
State/province [211] 0 0
Haryana
Country [212] 0 0
India
State/province [212] 0 0
Karnataka
Country [213] 0 0
India
State/province [213] 0 0
Madhya Pradesh
Country [214] 0 0
India
State/province [214] 0 0
Maharashtra
Country [215] 0 0
India
State/province [215] 0 0
Maharastra
Country [216] 0 0
India
State/province [216] 0 0
Punjab
Country [217] 0 0
India
State/province [217] 0 0
Rajasthan
Country [218] 0 0
India
State/province [218] 0 0
Tamil Nadu
Country [219] 0 0
India
State/province [219] 0 0
Tamilnadu
Country [220] 0 0
India
State/province [220] 0 0
Uttar Pradesh
Country [221] 0 0
India
State/province [221] 0 0
Bangalore, Karnataka
Country [222] 0 0
India
State/province [222] 0 0
Bikaner
Country [223] 0 0
India
State/province [223] 0 0
Mangalore
Country [224] 0 0
India
State/province [224] 0 0
New Delhi
Country [225] 0 0
India
State/province [225] 0 0
Pune
Country [226] 0 0
Israel
State/province [226] 0 0
Afula
Country [227] 0 0
Israel
State/province [227] 0 0
Ashkelon
Country [228] 0 0
Israel
State/province [228] 0 0
Hadera
Country [229] 0 0
Israel
State/province [229] 0 0
Haifa
Country [230] 0 0
Israel
State/province [230] 0 0
Jerusalem
Country [231] 0 0
Israel
State/province [231] 0 0
Kfar-Saba
Country [232] 0 0
Israel
State/province [232] 0 0
Nahariya
Country [233] 0 0
Israel
State/province [233] 0 0
Nazareth
Country [234] 0 0
Israel
State/province [234] 0 0
Petach Tikva
Country [235] 0 0
Israel
State/province [235] 0 0
Rehovot
Country [236] 0 0
Israel
State/province [236] 0 0
Safed
Country [237] 0 0
Israel
State/province [237] 0 0
Tel Aviv
Country [238] 0 0
Israel
State/province [238] 0 0
Tiberias
Country [239] 0 0
Italy
State/province [239] 0 0
Ascoli Piceno
Country [240] 0 0
Italy
State/province [240] 0 0
Bergamo
Country [241] 0 0
Italy
State/province [241] 0 0
Chieti
Country [242] 0 0
Italy
State/province [242] 0 0
Foggia
Country [243] 0 0
Italy
State/province [243] 0 0
Gravedona (Co)
Country [244] 0 0
Italy
State/province [244] 0 0
Grosseto
Country [245] 0 0
Italy
State/province [245] 0 0
Massa
Country [246] 0 0
Italy
State/province [246] 0 0
Milano
Country [247] 0 0
Italy
State/province [247] 0 0
Milan
Country [248] 0 0
Italy
State/province [248] 0 0
Naples
Country [249] 0 0
Italy
State/province [249] 0 0
Novara
Country [250] 0 0
Italy
State/province [250] 0 0
Pavia
Country [251] 0 0
Italy
State/province [251] 0 0
Perugia
Country [252] 0 0
Italy
State/province [252] 0 0
Roma
Country [253] 0 0
Italy
State/province [253] 0 0
San Daniele Del Friuli (Udine)
Country [254] 0 0
Italy
State/province [254] 0 0
Saronno (Va)
Country [255] 0 0
Italy
State/province [255] 0 0
Verona
Country [256] 0 0
Japan
State/province [256] 0 0
Aichi
Country [257] 0 0
Japan
State/province [257] 0 0
Chiba
Country [258] 0 0
Japan
State/province [258] 0 0
Fukuoka
Country [259] 0 0
Japan
State/province [259] 0 0
Gifu
Country [260] 0 0
Japan
State/province [260] 0 0
Hiroshima
Country [261] 0 0
Japan
State/province [261] 0 0
Hokkaido
Country [262] 0 0
Japan
State/province [262] 0 0
Ibaraki
Country [263] 0 0
Japan
State/province [263] 0 0
Ishikawa
Country [264] 0 0
Japan
State/province [264] 0 0
Kagoshima
Country [265] 0 0
Japan
State/province [265] 0 0
Kanagawa
Country [266] 0 0
Japan
State/province [266] 0 0
Nagano
Country [267] 0 0
Japan
State/province [267] 0 0
Oita
Country [268] 0 0
Japan
State/province [268] 0 0
Osaka
Country [269] 0 0
Japan
State/province [269] 0 0
Saga
Country [270] 0 0
Japan
State/province [270] 0 0
Saitama
Country [271] 0 0
Japan
State/province [271] 0 0
Tokushima
Country [272] 0 0
Japan
State/province [272] 0 0
Tokyo
Country [273] 0 0
Japan
State/province [273] 0 0
Yamaguchi
Country [274] 0 0
Japan
State/province [274] 0 0
Kochi
Country [275] 0 0
Japan
State/province [275] 0 0
Kumamoto
Country [276] 0 0
Japan
State/province [276] 0 0
Kyoto
Country [277] 0 0
Korea, Republic of
State/province [277] 0 0
Gangwon-Do
Country [278] 0 0
Korea, Republic of
State/province [278] 0 0
Gyeongangnam-Do
Country [279] 0 0
Korea, Republic of
State/province [279] 0 0
Gyeonggi-Do
Country [280] 0 0
Korea, Republic of
State/province [280] 0 0
Gyeongsangam-Do
Country [281] 0 0
Korea, Republic of
State/province [281] 0 0
Daegu
Country [282] 0 0
Korea, Republic of
State/province [282] 0 0
Goyang
Country [283] 0 0
Korea, Republic of
State/province [283] 0 0
Gwangju
Country [284] 0 0
Korea, Republic of
State/province [284] 0 0
Incheon
Country [285] 0 0
Korea, Republic of
State/province [285] 0 0
Jeonbuk
Country [286] 0 0
Korea, Republic of
State/province [286] 0 0
Pusan
Country [287] 0 0
Korea, Republic of
State/province [287] 0 0
Seoul
Country [288] 0 0
Korea, Republic of
State/province [288] 0 0
Suwon
Country [289] 0 0
Mexico
State/province [289] 0 0
Baja Californa Sur
Country [290] 0 0
Mexico
State/province [290] 0 0
Baja California
Country [291] 0 0
Mexico
State/province [291] 0 0
Coahuila
Country [292] 0 0
Mexico
State/province [292] 0 0
Estado De Mexico
Country [293] 0 0
Mexico
State/province [293] 0 0
Guerrero
Country [294] 0 0
Mexico
State/province [294] 0 0
Hidalgo
Country [295] 0 0
Mexico
State/province [295] 0 0
Jalisco
Country [296] 0 0
Mexico
State/province [296] 0 0
Nuevo Leon
Country [297] 0 0
Mexico
State/province [297] 0 0
Sinaloa
Country [298] 0 0
Mexico
State/province [298] 0 0
Veracruz
Country [299] 0 0
Mexico
State/province [299] 0 0
Aguascalientes
Country [300] 0 0
Mexico
State/province [300] 0 0
Chihuahua
Country [301] 0 0
Mexico
State/province [301] 0 0
Durango
Country [302] 0 0
Mexico
State/province [302] 0 0
Queretaro
Country [303] 0 0
Mexico
State/province [303] 0 0
San Luis Potosi
Country [304] 0 0
Netherlands
State/province [304] 0 0
Alkmaar
Country [305] 0 0
Netherlands
State/province [305] 0 0
Almere
Country [306] 0 0
Netherlands
State/province [306] 0 0
Amsterdam
Country [307] 0 0
Netherlands
State/province [307] 0 0
Beverwijk
Country [308] 0 0
Netherlands
State/province [308] 0 0
Boxmeer
Country [309] 0 0
Netherlands
State/province [309] 0 0
Den Haag
Country [310] 0 0
Netherlands
State/province [310] 0 0
Dirksland
Country [311] 0 0
Netherlands
State/province [311] 0 0
Ede
Country [312] 0 0
Netherlands
State/province [312] 0 0
Goes
Country [313] 0 0
Netherlands
State/province [313] 0 0
Gouda
Country [314] 0 0
Netherlands
State/province [314] 0 0
Heerlen
Country [315] 0 0
Netherlands
State/province [315] 0 0
Hilversum
Country [316] 0 0
Netherlands
State/province [316] 0 0
Maastrict
Country [317] 0 0
Netherlands
State/province [317] 0 0
Meppel
Country [318] 0 0
Netherlands
State/province [318] 0 0
Purmerend
Country [319] 0 0
Netherlands
State/province [319] 0 0
Sneek
Country [320] 0 0
Netherlands
State/province [320] 0 0
Veldhoven
Country [321] 0 0
Netherlands
State/province [321] 0 0
Weert
Country [322] 0 0
Netherlands
State/province [322] 0 0
Zwolle
Country [323] 0 0
New Zealand
State/province [323] 0 0
Auckland
Country [324] 0 0
New Zealand
State/province [324] 0 0
Christchurch
Country [325] 0 0
New Zealand
State/province [325] 0 0
Hastings
Country [326] 0 0
New Zealand
State/province [326] 0 0
Nelson
Country [327] 0 0
New Zealand
State/province [327] 0 0
Palmerston North
Country [328] 0 0
Norway
State/province [328] 0 0
Bergen
Country [329] 0 0
Norway
State/province [329] 0 0
Bodo
Country [330] 0 0
Norway
State/province [330] 0 0
Drammen
Country [331] 0 0
Norway
State/province [331] 0 0
Hamar
Country [332] 0 0
Norway
State/province [332] 0 0
Kongsvinger
Country [333] 0 0
Norway
State/province [333] 0 0
Kristiansund
Country [334] 0 0
Norway
State/province [334] 0 0
Lillehammer
Country [335] 0 0
Norway
State/province [335] 0 0
Oslo
Country [336] 0 0
Norway
State/province [336] 0 0
Stavanger
Country [337] 0 0
Norway
State/province [337] 0 0
Tynset
Country [338] 0 0
Peru
State/province [338] 0 0
Callao
Country [339] 0 0
Peru
State/province [339] 0 0
Lambayeque
Country [340] 0 0
Peru
State/province [340] 0 0
Cusco
Country [341] 0 0
Peru
State/province [341] 0 0
Ica
Country [342] 0 0
Peru
State/province [342] 0 0
Lima
Country [343] 0 0
Poland
State/province [343] 0 0
Mazowiekie
Country [344] 0 0
Poland
State/province [344] 0 0
Bialystok
Country [345] 0 0
Poland
State/province [345] 0 0
Bydgoszcz
Country [346] 0 0
Poland
State/province [346] 0 0
Bytom
Country [347] 0 0
Poland
State/province [347] 0 0
Czestochowa
Country [348] 0 0
Poland
State/province [348] 0 0
Elblag
Country [349] 0 0
Poland
State/province [349] 0 0
Gdynia
Country [350] 0 0
Poland
State/province [350] 0 0
Grodzisk Mazowiecki
Country [351] 0 0
Poland
State/province [351] 0 0
Inowroclaw
Country [352] 0 0
Poland
State/province [352] 0 0
Kielce
Country [353] 0 0
Poland
State/province [353] 0 0
Koscierzyna
Country [354] 0 0
Poland
State/province [354] 0 0
Krakow
Country [355] 0 0
Poland
State/province [355] 0 0
Lodz
Country [356] 0 0
Poland
State/province [356] 0 0
Lublin
Country [357] 0 0
Poland
State/province [357] 0 0
Opole
Country [358] 0 0
Poland
State/province [358] 0 0
Ostrowiec Swietokrzyski
Country [359] 0 0
Poland
State/province [359] 0 0
Plock
Country [360] 0 0
Poland
State/province [360] 0 0
Poznan
Country [361] 0 0
Poland
State/province [361] 0 0
Radom
Country [362] 0 0
Poland
State/province [362] 0 0
Rzeszow
Country [363] 0 0
Poland
State/province [363] 0 0
Slupsk
Country [364] 0 0
Poland
State/province [364] 0 0
Szczecin
Country [365] 0 0
Poland
State/province [365] 0 0
Tarnow
Country [366] 0 0
Poland
State/province [366] 0 0
Torun
Country [367] 0 0
Poland
State/province [367] 0 0
Warsaw
Country [368] 0 0
Poland
State/province [368] 0 0
Warszawa
Country [369] 0 0
Poland
State/province [369] 0 0
Wloclawek
Country [370] 0 0
Poland
State/province [370] 0 0
Zabrze
Country [371] 0 0
Poland
State/province [371] 0 0
Zielona Gora
Country [372] 0 0
Puerto Rico
State/province [372] 0 0
Cidra
Country [373] 0 0
Puerto Rico
State/province [373] 0 0
San Juan
Country [374] 0 0
Romania
State/province [374] 0 0
Arad
Country [375] 0 0
Romania
State/province [375] 0 0
Baia Mare
Country [376] 0 0
Romania
State/province [376] 0 0
Braila
Country [377] 0 0
Romania
State/province [377] 0 0
Bucharest
Country [378] 0 0
Romania
State/province [378] 0 0
Craiova
Country [379] 0 0
Romania
State/province [379] 0 0
Oradea
Country [380] 0 0
Romania
State/province [380] 0 0
Pitesti
Country [381] 0 0
Romania
State/province [381] 0 0
Sibiu
Country [382] 0 0
Romania
State/province [382] 0 0
Targu Mures
Country [383] 0 0
Romania
State/province [383] 0 0
Timisoara
Country [384] 0 0
Russian Federation
State/province [384] 0 0
Barnaul
Country [385] 0 0
Russian Federation
State/province [385] 0 0
Chelyabinsk
Country [386] 0 0
Russian Federation
State/province [386] 0 0
Ekaterinburg
Country [387] 0 0
Russian Federation
State/province [387] 0 0
Kaluga
Country [388] 0 0
Russian Federation
State/province [388] 0 0
Kazan
Country [389] 0 0
Russian Federation
State/province [389] 0 0
Kemerovo
Country [390] 0 0
Russian Federation
State/province [390] 0 0
Krasnoyarsk
Country [391] 0 0
Russian Federation
State/province [391] 0 0
Moscow Reg. Zhekeznodorozhniy
Country [392] 0 0
Russian Federation
State/province [392] 0 0
Moscow
Country [393] 0 0
Russian Federation
State/province [393] 0 0
Nizhni Novgorod
Country [394] 0 0
Russian Federation
State/province [394] 0 0
Nizhny Novgorod
Country [395] 0 0
Russian Federation
State/province [395] 0 0
Novosibirsk
Country [396] 0 0
Russian Federation
State/province [396] 0 0
Odintsovo
Country [397] 0 0
Russian Federation
State/province [397] 0 0
Penza
Country [398] 0 0
Russian Federation
State/province [398] 0 0
Perm
Country [399] 0 0
Russian Federation
State/province [399] 0 0
Rostov-On-Don
Country [400] 0 0
Russian Federation
State/province [400] 0 0
Ryazan
Country [401] 0 0
Russian Federation
State/province [401] 0 0
Saint Petersburg
Country [402] 0 0
Russian Federation
State/province [402] 0 0
Saint-Petersburg
Country [403] 0 0
Russian Federation
State/province [403] 0 0
Saratov
Country [404] 0 0
Russian Federation
State/province [404] 0 0
St. Petersburg
Country [405] 0 0
Russian Federation
State/province [405] 0 0
Tomsk
Country [406] 0 0
Russian Federation
State/province [406] 0 0
Tver
Country [407] 0 0
Russian Federation
State/province [407] 0 0
Tyumen
Country [408] 0 0
Russian Federation
State/province [408] 0 0
Vasilievsky Island
Country [409] 0 0
Russian Federation
State/province [409] 0 0
Voronezh
Country [410] 0 0
Russian Federation
State/province [410] 0 0
Yaroslavl
Country [411] 0 0
Russian Federation
State/province [411] 0 0
Zhukovskiy
Country [412] 0 0
Singapore
State/province [412] 0 0
Singapore
Country [413] 0 0
Slovakia
State/province [413] 0 0
Banska Bystrica
Country [414] 0 0
Slovakia
State/province [414] 0 0
Bratislava
Country [415] 0 0
Slovakia
State/province [415] 0 0
Kosice
Country [416] 0 0
Slovakia
State/province [416] 0 0
Kralovsky Chlmec
Country [417] 0 0
Slovakia
State/province [417] 0 0
Liptovsky Hradok
Country [418] 0 0
Slovakia
State/province [418] 0 0
Lucenec
Country [419] 0 0
Slovakia
State/province [419] 0 0
Martin
Country [420] 0 0
Slovakia
State/province [420] 0 0
Nitra
Country [421] 0 0
South Africa
State/province [421] 0 0
Eastern Cape
Country [422] 0 0
South Africa
State/province [422] 0 0
Free State
Country [423] 0 0
South Africa
State/province [423] 0 0
Gauteng
Country [424] 0 0
South Africa
State/province [424] 0 0
Kwa Zulu Natal
Country [425] 0 0
South Africa
State/province [425] 0 0
Western Cape
Country [426] 0 0
South Africa
State/province [426] 0 0
Johannesburg
Country [427] 0 0
Spain
State/province [427] 0 0
Alicante
Country [428] 0 0
Spain
State/province [428] 0 0
Asturas
Country [429] 0 0
Spain
State/province [429] 0 0
Gerona
Country [430] 0 0
Spain
State/province [430] 0 0
Madrid
Country [431] 0 0
Spain
State/province [431] 0 0
Almeria
Country [432] 0 0
Spain
State/province [432] 0 0
Barcelona
Country [433] 0 0
Spain
State/province [433] 0 0
Caceres
Country [434] 0 0
Spain
State/province [434] 0 0
El Ejido
Country [435] 0 0
Spain
State/province [435] 0 0
Granada
Country [436] 0 0
Spain
State/province [436] 0 0
Lleida
Country [437] 0 0
Spain
State/province [437] 0 0
Lugo
Country [438] 0 0
Spain
State/province [438] 0 0