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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00412984
Registration number
NCT00412984
Ethics application status
Date submitted
18/12/2006
Date registered
19/12/2006
Date last updated
3/07/2018
Titles & IDs
Public title
Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation
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Scientific title
A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind, Parallel Arm Study to Evaluate Efficacy and Safety of Apixaban in Preventing Stroke and Systemic Embolism in Subjects With Nonvalvular Atrial Fibrillation
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Secondary ID [1]
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CV185-030
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Universal Trial Number (UTN)
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Trial acronym
ARISTOTLE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation
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Atrial Flutter
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Condition category
Condition code
Cardiovascular
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Other cardiovascular diseases
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Cardiovascular
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0
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Coronary heart disease
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - warfarin
Treatment: Drugs - apixaban
Active comparator: 1 -
Experimental: 2 -
Treatment: Drugs: warfarin
Oral tablets, 2.0 mg, adjusted to an INR of 2.5 (range 2.0 to 3.0)
Treatment: Drugs: apixaban
Oral tablets, 5.0 mg or 2.5 mg, twice daily
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period
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Assessment method [1]
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All suspected efficacy events were adjudicated by the Central Events Committee (CEC). Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.
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Timepoint [1]
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Time to first event in "Intended Treatment Period": started on day of randomization, ended at efficacy cut-off date (date target number of primary efficacy events [448] was expected to have occurred; set to 30-Jan-2011, prior to unblinding).
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Primary outcome [2]
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Rate of Adjudicated Stroke or Systemic Embolism (SE) During the Intended Treatment Period
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Assessment method [2]
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Rate=Number of adjudicated stroke or SE events per 100 patient years. Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.
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Timepoint [2]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [1]
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Number of Participants With Event of Major (International Society on Thrombosis and Hemostasis [ISTH]) Bleeding During Treatment Period
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Assessment method [1]
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ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more, and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.
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Timepoint [1]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Secondary outcome [2]
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Rate of Adjudicated Major (ISTH) Bleed Events During Treatment Period
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Assessment method [2]
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Rate=number of adjudicated major (ISTH) bleed events per 100 patient years. ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.
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Timepoint [2]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Secondary outcome [3]
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Number of Participants With Events of All-Cause Death During the Intended Treatment Period
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Assessment method [3]
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Death was defined as all-cause mortality. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, myocardial infarction (MI), sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).
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Timepoint [3]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [4]
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Rate of Adjudicated All-Cause Death During the Intended Treatment Period
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Assessment method [4]
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All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, MI, sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).
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Timepoint [4]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [5]
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Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period
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Assessment method [5]
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Diagnosis for an acute or evolving MI=elevation of creatine kinase-MB isoenzyme (CK-MB) or Troponin T or I = 2 × the upper limit of normal (ULN), or if no CK-MB or troponin values are available, a total CK = 2×ULN, or new, significant (=0.04 s) Q waves in =2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1.
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Timepoint [5]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [6]
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Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period
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Assessment method [6]
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Diagnosis for an acute or evolving MI=elevation of CK-MB or Troponin T or I = 2 × the ULN, or if no CK-MB or troponin values are available, a total CK = 2×ULN, or new, significant (=0.04 s) Q waves in =2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1. For description of ACD, see Outcome Measure 5.
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Timepoint [6]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [7]
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Number of Warfarin/Vitamin K Antagonist (VKA) Naive Participants With Composite Stroke / Systemic Embolism (SE) / Major Bleeding During the Intended Treatment Period
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Assessment method [7]
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For descriptions of Stroke and SE, see Outcome Measure 1. For description of Major bleeding, see Outcome Measure 3.
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Timepoint [7]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [8]
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Rate of Composite Stroke / Systemic Embolism / Major Bleeding in Warfarin/Vitamin K Antagonist (VKA) Naive Participants During the Intended Treatment Period
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Assessment method [8]
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Timepoint [8]
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"Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).
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Secondary outcome [9]
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Number of Participants With Events of Major or Clinically Relevant Nonmajor (CRNM) Bleed During Treatment Period
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Assessment method [9]
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Major bleeding=bleeding that is clinically overt and that either resulted in a decrease in hemoglobin of 2 g/dL or more over a 24-hour period, led to a transfusion of 2 or more units of packed red blood cells, occurred in a critical site, or led to death. CRNM bleeding=bleeding that is clinically overt, that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event, that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.
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Timepoint [9]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Secondary outcome [10]
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Rate of Events of Major or Clinically Relevant Non-Major (CRNM) Bleed During Treatment Period
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Assessment method [10]
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Rate=number of major or CRNM bleed events per 100 patient years. Major=clinically overt and either 1) resulted in a decrease in hemoglobin of 2 g/dL or more, or 2) led to a transfusion of 2 or more units of packed red blood cells, or 3) occurred in a critical site, or 4) led to death. CRNM bleeding=clinically overt, but satisfied no additional criteria required to be adjudicated as a major bleeding event, and led to either 1) hospital admission for bleeding or 2) physician guided medical or surgical treatment for bleeding or 3) a change in antithrombotic therapy.
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Timepoint [10]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Secondary outcome [11]
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Number of Participants With All Bleeding Events During Treatment Period
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Assessment method [11]
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All bleeding events include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.
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Timepoint [11]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Secondary outcome [12]
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Rate of All Bleeding Events During Treatment Period
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Assessment method [12]
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Rate=number of all bleeding events per 100 patient years. "All bleeding events" include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.
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Timepoint [12]
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"Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.
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Eligibility
Key inclusion criteria
* Males and females = 18 yrs with atrial fibrillation (AF) and one or more of the following risk factors for stroke:
* Age = 75, previous stroke
* transient ischemic attack (TIA) or Systemic Embolism (SE)
* Symptomatic congestive heart failure or left ventricular dysfunction with left ventricular ejection fraction (LVEF) = 40%
* Diabetes mellitus or hypertension requiring pharmacological treatment
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Minimum age
No limit
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
31/12/2006
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
25/05/2011
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Sample size
Target
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Accrual to date
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Final
20976
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Local Institution - Coffs Harbour
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Recruitment hospital [2]
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Local Institution - Concord
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Recruitment hospital [3]
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Local Institution - Gosford
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Recruitment hospital [4]
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Local Institution - Kogarah
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Local Institution - Miranda
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Recruitment hospital [6]
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Local Institution - Auchenflower
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Recruitment hospital [7]
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Local Institution - Brisbane
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Recruitment hospital [8]
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Local Institution - Caboolture
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Recruitment hospital [9]
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Local Institution - Herston
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Recruitment hospital [10]
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Local Institution - Kippa Ring
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Recruitment hospital [11]
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Local Institution - Nambour
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Recruitment hospital [12]
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Local Institution - Sherwood
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Recruitment hospital [13]
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Local Institution - Adelaide
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Recruitment hospital [14]
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Local Institution - Ashford
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Recruitment hospital [15]
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Local Institution - Bedford Park
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Recruitment hospital [16]
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Local Institution - Woodville
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Recruitment hospital [17]
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Local Institution - Box Hill
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Recruitment hospital [18]
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Local Institution - Dandenong
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Recruitment hospital [19]
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Local Institution - Geelong
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Recruitment hospital [20]
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Local Institution - Fremantle
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Recruitment hospital [21]
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Local Institution - Joondalup
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Recruitment postcode(s) [1]
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2450 - Coffs Harbour
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Recruitment postcode(s) [2]
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2139 - Concord
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Recruitment postcode(s) [3]
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2250 - Gosford
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Recruitment postcode(s) [4]
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2217 - Kogarah
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Recruitment postcode(s) [5]
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2228 - Miranda
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Recruitment postcode(s) [6]
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4066 - Auchenflower
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Recruitment postcode(s) [7]
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4032 - Brisbane
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Recruitment postcode(s) [8]
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4510 - Caboolture
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Recruitment postcode(s) [9]
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4029 - Herston
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Recruitment postcode(s) [10]
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4021 - Kippa Ring
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Recruitment postcode(s) [11]
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4560 - Nambour
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Recruitment postcode(s) [12]
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4075 - Sherwood
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Recruitment postcode(s) [13]
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SA 5000 - Adelaide
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Recruitment postcode(s) [14]
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5035 - Ashford
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Recruitment postcode(s) [15]
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5042 - Bedford Park
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Recruitment postcode(s) [16]
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5011 - Woodville
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Recruitment postcode(s) [17]
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3128 - Box Hill
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Recruitment postcode(s) [18]
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3175 - Dandenong
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Recruitment postcode(s) [19]
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3220 - Geelong
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Recruitment postcode(s) [20]
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6160 - Fremantle
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Recruitment postcode(s) [21]
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6027 - Joondalup
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Recruitment outside Australia
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Alabama
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Alaska
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Arizona
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Colorado
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Connecticut
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Delaware
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Florida
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Buenos Aires
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Provincia DE Cordoba
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RIO Negro
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Santa FE
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Graz
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Country [55]
0
0
Austria
Query!
State/province [55]
0
0
Oberpullendorf
Query!
Country [56]
0
0
Austria
Query!
State/province [56]
0
0
Vienna
Query!
Country [57]
0
0
Belgium
Query!
State/province [57]
0
0
Aalst
Query!
Country [58]
0
0
Belgium
Query!
State/province [58]
0
0
Antwerpen
Query!
Country [59]
0
0
Belgium
Query!
State/province [59]
0
0
Arlon
Query!
Country [60]
0
0
Belgium
Query!
State/province [60]
0
0
Brugge
Query!
Country [61]
0
0
Belgium
Query!
State/province [61]
0
0
Brussels
Query!
Country [62]
0
0
Belgium
Query!
State/province [62]
0
0
Dillingen
Query!
Country [63]
0
0
Belgium
Query!
State/province [63]
0
0
Genk
Query!
Country [64]
0
0
Belgium
Query!
State/province [64]
0
0
Gent
Query!
Country [65]
0
0
Belgium
Query!
State/province [65]
0
0
Gilly
Query!
Country [66]
0
0
Belgium
Query!
State/province [66]
0
0
Hasselt
Query!
Country [67]
0
0
Belgium
Query!
State/province [67]
0
0
Huy
Query!
Country [68]
0
0
Belgium
Query!
State/province [68]
0
0
Kortrijk
Query!
Country [69]
0
0
Belgium
Query!
State/province [69]
0
0
Menen
Query!
Country [70]
0
0
Belgium
Query!
State/province [70]
0
0
Mol
Query!
Country [71]
0
0
Belgium
Query!
State/province [71]
0
0
Montegnee
Query!
Country [72]
0
0
Belgium
Query!
State/province [72]
0
0
Verviers
Query!
Country [73]
0
0
Belgium
Query!
State/province [73]
0
0
Woluwe- Saint Lambert
Query!
Country [74]
0
0
Belgium
Query!
State/province [74]
0
0
Yvoir
Query!
Country [75]
0
0
Brazil
Query!
State/province [75]
0
0
Bahia
Query!
Country [76]
0
0
Brazil
Query!
State/province [76]
0
0
Minas Gerais
Query!
Country [77]
0
0
Brazil
Query!
State/province [77]
0
0
Parana
Query!
Country [78]
0
0
Brazil
Query!
State/province [78]
0
0
Para
Query!
Country [79]
0
0
Brazil
Query!
State/province [79]
0
0
RIO Grande DO Norte
Query!
Country [80]
0
0
Brazil
Query!
State/province [80]
0
0
Rio Grande Do Norte
Query!
Country [81]
0
0
Brazil
Query!
State/province [81]
0
0
RIO Grande DO SUL
Query!
Country [82]
0
0
Brazil
Query!
State/province [82]
0
0
Rio Grande Do Sul
Query!
Country [83]
0
0
Brazil
Query!
State/province [83]
0
0
Santa Catarina
Query!
Country [84]
0
0
Brazil
Query!
State/province [84]
0
0
SAO Paulo
Query!
Country [85]
0
0
Brazil
Query!
State/province [85]
0
0
Sao Paulo
Query!
Country [86]
0
0
Brazil
Query!
State/province [86]
0
0
Rio De Janeiro
Query!
Country [87]
0
0
Canada
Query!
State/province [87]
0
0
Alberta
Query!
Country [88]
0
0
Canada
Query!
State/province [88]
0
0
British Columbia
Query!
Country [89]
0
0
Canada
Query!
State/province [89]
0
0
Manitoba
Query!
Country [90]
0
0
Canada
Query!
State/province [90]
0
0
New Brunswick
Query!
Country [91]
0
0
Canada
Query!
State/province [91]
0
0
Newfoundland and Labrador
Query!
Country [92]
0
0
Canada
Query!
State/province [92]
0
0
Ontario
Query!
Country [93]
0
0
Canada
Query!
State/province [93]
0
0
Prince Edward Island
Query!
Country [94]
0
0
Canada
Query!
State/province [94]
0
0
Quebec
Query!
Country [95]
0
0
Canada
Query!
State/province [95]
0
0
Saskatchewan
Query!
Country [96]
0
0
Chile
Query!
State/province [96]
0
0
LOS Lagos
Query!
Country [97]
0
0
Chile
Query!
State/province [97]
0
0
Metropolitana
Query!
Country [98]
0
0
Chile
Query!
State/province [98]
0
0
Region De La Araucania
Query!
Country [99]
0
0
Chile
Query!
State/province [99]
0
0
Region DE LA Araucania
Query!
Country [100]
0
0
Chile
Query!
State/province [100]
0
0
Valparaiso
Query!
Country [101]
0
0
China
Query!
State/province [101]
0
0
Beijing
Query!
Country [102]
0
0
China
Query!
State/province [102]
0
0
Gansu
Query!
Country [103]
0
0
China
Query!
State/province [103]
0
0
Guangdong
Query!
Country [104]
0
0
China
Query!
State/province [104]
0
0
Hebei
Query!
Country [105]
0
0
China
Query!
State/province [105]
0
0
Heilongjiang
Query!
Country [106]
0
0
China
Query!
State/province [106]
0
0
Hubei
Query!
Country [107]
0
0
China
Query!
State/province [107]
0
0
Hunan
Query!
Country [108]
0
0
China
Query!
State/province [108]
0
0
Jiangsu
Query!
Country [109]
0
0
China
Query!
State/province [109]
0
0
Liaoning
Query!
Country [110]
0
0
China
Query!
State/province [110]
0
0
Shandong
Query!
Country [111]
0
0
China
Query!
State/province [111]
0
0
Shanghai
Query!
Country [112]
0
0
China
Query!
State/province [112]
0
0
Sichuan
Query!
Country [113]
0
0
China
Query!
State/province [113]
0
0
Zhejiang
Query!
Country [114]
0
0
Colombia
Query!
State/province [114]
0
0
Antioquia
Query!
Country [115]
0
0
Colombia
Query!
State/province [115]
0
0
Barranquilla
Query!
Country [116]
0
0
Colombia
Query!
State/province [116]
0
0
Bogota
Query!
Country [117]
0
0
Colombia
Query!
State/province [117]
0
0
Cali
Query!
Country [118]
0
0
Colombia
Query!
State/province [118]
0
0
Medellin
Query!
Country [119]
0
0
Czechia
Query!
State/province [119]
0
0
Boskovice
Query!
Country [120]
0
0
Czechia
Query!
State/province [120]
0
0
Brno-Malomerice
Query!
Country [121]
0
0
Czechia
Query!
State/province [121]
0
0
Brno
Query!
Country [122]
0
0
Czechia
Query!
State/province [122]
0
0
Ivancice
Query!
Country [123]
0
0
Czechia
Query!
State/province [123]
0
0
Kladno
Query!
Country [124]
0
0
Czechia
Query!
State/province [124]
0
0
Litomysl
Query!
Country [125]
0
0
Czechia
Query!
State/province [125]
0
0
Mestec Kralove
Query!
Country [126]
0
0
Czechia
Query!
State/province [126]
0
0
Ostrava
Query!
Country [127]
0
0
Czechia
Query!
State/province [127]
0
0
Prague 13
Query!
Country [128]
0
0
Czechia
Query!
State/province [128]
0
0
Prague 2
Query!
Country [129]
0
0
Czechia
Query!
State/province [129]
0
0
Pribram
Query!
Country [130]
0
0
Czechia
Query!
State/province [130]
0
0
Usti Nad Orlici
Query!
Country [131]
0
0
Denmark
Query!
State/province [131]
0
0
Arhus C
Query!
Country [132]
0
0
Denmark
Query!
State/province [132]
0
0
Esbjerg
Query!
Country [133]
0
0
Denmark
Query!
State/province [133]
0
0
Frederiksberg
Query!
Country [134]
0
0
Denmark
Query!
State/province [134]
0
0
Frederikssund
Query!
Country [135]
0
0
Denmark
Query!
State/province [135]
0
0
Gentofte
Query!
Country [136]
0
0
Denmark
Query!
State/province [136]
0
0
Haderslev
Query!
Country [137]
0
0
Denmark
Query!
State/province [137]
0
0
Hellerup
Query!
Country [138]
0
0
Denmark
Query!
State/province [138]
0
0
Herlev
Query!
Country [139]
0
0
Denmark
Query!
State/province [139]
0
0
Herning
Query!
Country [140]
0
0
Denmark
Query!
State/province [140]
0
0
Hillerod
Query!
Country [141]
0
0
Denmark
Query!
State/province [141]
0
0
Hvidovre
Query!
Country [142]
0
0
Denmark
Query!
State/province [142]
0
0
Kobenhavn
Query!
Country [143]
0
0
Denmark
Query!
State/province [143]
0
0
Kolding
Query!
Country [144]
0
0
Denmark
Query!
State/province [144]
0
0
Odense
Query!
Country [145]
0
0
Denmark
Query!
State/province [145]
0
0
Silkeborg
Query!
Country [146]
0
0
Denmark
Query!
State/province [146]
0
0
Slagelse
Query!
Country [147]
0
0
Denmark
Query!
State/province [147]
0
0
Svendborg
Query!
Country [148]
0
0
Finland
Query!
State/province [148]
0
0
Helsinki
Query!
Country [149]
0
0
Finland
Query!
State/province [149]
0
0
Hus
Query!
Country [150]
0
0
Finland
Query!
State/province [150]
0
0
Jyvaskyla
Query!
Country [151]
0
0
Finland
Query!
State/province [151]
0
0
Kemi
Query!
Country [152]
0
0
Finland
Query!
State/province [152]
0
0
Oulu
Query!
Country [153]
0
0
Finland
Query!
State/province [153]
0
0
Pori
Query!
Country [154]
0
0
Finland
Query!
State/province [154]
0
0
Tampere
Query!
Country [155]
0
0
France
Query!
State/province [155]
0
0
Amiens Cedex 1
Query!
Country [156]
0
0
France
Query!
State/province [156]
0
0
Bordeaux Cedex
Query!
Country [157]
0
0
France
Query!
State/province [157]
0
0
Brest
Query!
Country [158]
0
0
France
Query!
State/province [158]
0
0
Grenoble Cedex 09
Query!
Country [159]
0
0
France
Query!
State/province [159]
0
0
La Seyne Sur Mer
Query!
Country [160]
0
0
France
Query!
State/province [160]
0
0
Paris Cedex 18
Query!
Country [161]
0
0
France
Query!
State/province [161]
0
0
Six Fours Les Plages
Query!
Country [162]
0
0
Germany
Query!
State/province [162]
0
0
Aachen
Query!
Country [163]
0
0
Germany
Query!
State/province [163]
0
0
Bad Krozingen
Query!
Country [164]
0
0
Germany
Query!
State/province [164]
0
0
Bad Neustadt/ Salle
Query!
Country [165]
0
0
Germany
Query!
State/province [165]
0
0
Bad Oeynhausen
Query!
Country [166]
0
0
Germany
Query!
State/province [166]
0
0
Berlin-Kopenick
Query!
Country [167]
0
0
Germany
Query!
State/province [167]
0
0
Berlin
Query!
Country [168]
0
0
Germany
Query!
State/province [168]
0
0
Betzdorf
Query!
Country [169]
0
0
Germany
Query!
State/province [169]
0
0
Bochum
Query!
Country [170]
0
0
Germany
Query!
State/province [170]
0
0
Bonn
Query!
Country [171]
0
0
Germany
Query!
State/province [171]
0
0
Coburg
Query!
Country [172]
0
0
Germany
Query!
State/province [172]
0
0
Dillingen
Query!
Country [173]
0
0
Germany
Query!
State/province [173]
0
0
Dresden
Query!
Country [174]
0
0
Germany
Query!
State/province [174]
0
0
Duisburg
Query!
Country [175]
0
0
Germany
Query!
State/province [175]
0
0
Essen
Query!
Country [176]
0
0
Germany
Query!
State/province [176]
0
0
Frankfurt Am Main
Query!
Country [177]
0
0
Germany
Query!
State/province [177]
0
0
Gottingen
Query!
Country [178]
0
0
Germany
Query!
State/province [178]
0
0
Halle/Saale
Query!
Country [179]
0
0
Germany
Query!
State/province [179]
0
0
Hannover
Query!
Country [180]
0
0
Germany
Query!
State/province [180]
0
0
Heidelberg
Query!
Country [181]
0
0
Germany
Query!
State/province [181]
0
0
Kassel
Query!
Country [182]
0
0
Germany
Query!
State/province [182]
0
0
Lahr
Query!
Country [183]
0
0
Germany
Query!
State/province [183]
0
0
Ludwigshafen
Query!
Country [184]
0
0
Germany
Query!
State/province [184]
0
0
Mannheim
Query!
Country [185]
0
0
Germany
Query!
State/province [185]
0
0
Marburg
Query!
Country [186]
0
0
Germany
Query!
State/province [186]
0
0
Munchen
Query!
Country [187]
0
0
Germany
Query!
State/province [187]
0
0
Osnabruck
Query!
Country [188]
0
0
Germany
Query!
State/province [188]
0
0
Regensburg
Query!
Country [189]
0
0
Germany
Query!
State/province [189]
0
0
Riesa
Query!
Country [190]
0
0
Germany
Query!
State/province [190]
0
0
Rostiock
Query!
Country [191]
0
0
Germany
Query!
State/province [191]
0
0
Trier
Query!
Country [192]
0
0
Germany
Query!
State/province [192]
0
0
Waren
Query!
Country [193]
0
0
Germany
Query!
State/province [193]
0
0
Witten
Query!
Country [194]
0
0
Germany
Query!
State/province [194]
0
0
Wolmirstedt
Query!
Country [195]
0
0
Germany
Query!
State/province [195]
0
0
Worms
Query!
Country [196]
0
0
Hong Kong
Query!
State/province [196]
0
0
Hong Kong
Query!
Country [197]
0
0
Hong Kong
Query!
State/province [197]
0
0
Shatin
Query!
Country [198]
0
0
Hungary
Query!
State/province [198]
0
0
Budapest
Query!
Country [199]
0
0
Hungary
Query!
State/province [199]
0
0
Debrecen
Query!
Country [200]
0
0
Hungary
Query!
State/province [200]
0
0
Dunaujvaros
Query!
Country [201]
0
0
Hungary
Query!
State/province [201]
0
0
Gyor
Query!
Country [202]
0
0
Hungary
Query!
State/province [202]
0
0
Gyula
Query!
Country [203]
0
0
Hungary
Query!
State/province [203]
0
0
Hodmezovasarhely
Query!
Country [204]
0
0
Hungary
Query!
State/province [204]
0
0
Komarom
Query!
Country [205]
0
0
Hungary
Query!
State/province [205]
0
0
Mosonmagyarovar
Query!
Country [206]
0
0
Hungary
Query!
State/province [206]
0
0
Oroshaza
Query!
Country [207]
0
0
Hungary
Query!
State/province [207]
0
0
Pecs
Query!
Country [208]
0
0
Hungary
Query!
State/province [208]
0
0
Siofok
Query!
Country [209]
0
0
Hungary
Query!
State/province [209]
0
0
Sopron
Query!
Country [210]
0
0
Hungary
Query!
State/province [210]
0
0
Szentes
Query!
Country [211]
0
0
Hungary
Query!
State/province [211]
0
0
Zalaegerszeg
Query!
Country [212]
0
0
India
Query!
State/province [212]
0
0
Andhra Pradesh
Query!
Country [213]
0
0
India
Query!
State/province [213]
0
0
Andhrapradesh
Query!
Country [214]
0
0
India
Query!
State/province [214]
0
0
Andra Pradesh
Query!
Country [215]
0
0
India
Query!
State/province [215]
0
0
Gujarat
Query!
Country [216]
0
0
India
Query!
State/province [216]
0
0
Karnataka
Query!
Country [217]
0
0
India
Query!
State/province [217]
0
0
Kerela
Query!
Country [218]
0
0
India
Query!
State/province [218]
0
0
Maharashta
Query!
Country [219]
0
0
India
Query!
State/province [219]
0
0
Maharashtra
Query!
Country [220]
0
0
India
Query!
State/province [220]
0
0
Punjab
Query!
Country [221]
0
0
India
Query!
State/province [221]
0
0
Rajasthan
Query!
Country [222]
0
0
India
Query!
State/province [222]
0
0
Uttar Pradesh
Query!
Country [223]
0
0
India
Query!
State/province [223]
0
0
Ahmedabad
Query!
Country [224]
0
0
India
Query!
State/province [224]
0
0
Annamalainagar
Query!
Country [225]
0
0
India
Query!
State/province [225]
0
0
Bangalore
Query!
Country [226]
0
0
India
Query!
State/province [226]
0
0
Chennai
Query!
Country [227]
0
0
India
Query!
State/province [227]
0
0
Hyderabad
Query!
Country [228]
0
0
India
Query!
State/province [228]
0
0
Indore
Query!
Country [229]
0
0
India
Query!
State/province [229]
0
0
Kolkata
Query!
Country [230]
0
0
India
Query!
State/province [230]
0
0
Kottayam
Query!
Country [231]
0
0
India
Query!
State/province [231]
0
0
Lucknow
Query!
Country [232]
0
0
India
Query!
State/province [232]
0
0
Mumbai Naka
Query!
Country [233]
0
0
India
Query!
State/province [233]
0
0
Nashik
Query!
Country [234]
0
0
India
Query!
State/province [234]
0
0
New Delhi
Query!
Country [235]
0
0
India
Query!
State/province [235]
0
0
Pune
Query!
Country [236]
0
0
India
Query!
State/province [236]
0
0
Thrissur
Query!
Country [237]
0
0
India
Query!
State/province [237]
0
0
Vijayawada
Query!
Country [238]
0
0
Israel
Query!
State/province [238]
0
0
Afula
Query!
Country [239]
0
0
Israel
Query!
State/province [239]
0
0
Ashkelon
Query!
Country [240]
0
0
Israel
Query!
State/province [240]
0
0
Givatayim
Query!
Country [241]
0
0
Israel
Query!
State/province [241]
0
0
Hadera
Query!
Country [242]
0
0
Israel
Query!
State/province [242]
0
0
Haifa
Query!
Country [243]
0
0
Israel
Query!
State/province [243]
0
0
Holon
Query!
Country [244]
0
0
Israel
Query!
State/province [244]
0
0
Jerusalem
Query!
Country [245]
0
0
Israel
Query!
State/province [245]
0
0
Kfar-Saba
Query!
Country [246]
0
0
Israel
Query!
State/province [246]
0
0
Nazareth
Query!
Country [247]
0
0
Israel
Query!
State/province [247]
0
0
Petach-Tikva
Query!
Country [248]
0
0
Israel
Query!
State/province [248]
0
0
Safed
Query!
Country [249]
0
0
Israel
Query!
State/province [249]
0
0
Tel Aviv
Query!
Country [250]
0
0
Italy
Query!
State/province [250]
0
0
Lucca
Query!
Country [251]
0
0
Italy
Query!
State/province [251]
0
0
Ascoli Piceno
Query!
Country [252]
0
0
Italy
Query!
State/province [252]
0
0
Campobasso
Query!
Country [253]
0
0
Italy
Query!
State/province [253]
0
0
Chieti
Query!
Country [254]
0
0
Italy
Query!
State/province [254]
0
0
Cremona
Query!
Country [255]
0
0
Italy
Query!
State/province [255]
0
0
Fidenza (Pr)
Query!
Country [256]
0
0
Italy
Query!
State/province [256]
0
0
Genova
Query!
Country [257]
0
0
Italy
Query!
State/province [257]
0
0
Isernia
Query!
Country [258]
0
0
Italy
Query!
State/province [258]
0
0
Livorno
Query!
Country [259]
0
0
Italy
Query!
State/province [259]
0
0
Milano
Query!
Country [260]
0
0
Italy
Query!
State/province [260]
0
0
Napoli
Query!
Country [261]
0
0
Italy
Query!
State/province [261]
0
0
Palermo
Query!
Country [262]
0
0
Italy
Query!
State/province [262]
0
0
Reggio Emilia
Query!
Country [263]
0
0
Italy
Query!
State/province [263]
0
0
Roma
Query!
Country [264]
0
0
Italy
Query!
State/province [264]
0
0
San Daniele De Friuli
Query!
Country [265]
0
0
Italy
Query!
State/province [265]
0
0
Torino
Query!
Country [266]
0
0
Italy
Query!
State/province [266]
0
0
Vittorio Veneto (Tv)
Query!
Country [267]
0
0
Japan
Query!
State/province [267]
0
0
Fukuoka
Query!
Country [268]
0
0
Japan
Query!
State/province [268]
0
0
Fukushima
Query!
Country [269]
0
0
Japan
Query!
State/province [269]
0
0
Gunma
Query!
Country [270]
0
0
Japan
Query!
State/province [270]
0
0
Hokkaido
Query!
Country [271]
0
0
Japan
Query!
State/province [271]
0
0
Hyogo
Query!
Country [272]
0
0
Japan
Query!
State/province [272]
0
0
Kagoshima Prefecture
Query!
Country [273]
0
0
Japan
Query!
State/province [273]
0
0
Kanagawa
Query!
Country [274]
0
0
Japan
Query!
State/province [274]
0
0
Miyagi
Query!
Country [275]
0
0
Japan
Query!
State/province [275]
0
0
Nara
Query!
Country [276]
0
0
Japan
Query!
State/province [276]
0
0
Osaka
Query!
Country [277]
0
0
Japan
Query!
State/province [277]
0
0
Saga
Query!
Country [278]
0
0
Japan
Query!
State/province [278]
0
0
Saitama
Query!
Country [279]
0
0
Japan
Query!
State/province [279]
0
0
Tokyo
Query!
Country [280]
0
0
Japan
Query!
State/province [280]
0
0
Toyama
Query!
Country [281]
0
0
Japan
Query!
State/province [281]
0
0
Yamaguchi
Query!
Country [282]
0
0
Japan
Query!
State/province [282]
0
0
Fukui
Query!
Country [283]
0
0
Japan
Query!
State/province [283]
0
0
Kagoshima
Query!
Country [284]
0
0
Japan
Query!
State/province [284]
0
0
Kyoto
Query!
Country [285]
0
0
Japan
Query!
State/province [285]
0
0
Nagasaki
Query!
Country [286]
0
0
Japan
Query!
State/province [286]
0
0
Oita
Query!
Country [287]
0
0
Korea, Republic of
Query!
State/province [287]
0
0
Gyeonggi-Do
Query!
Country [288]
0
0
Korea, Republic of
Query!
State/province [288]
0
0
Korea
Query!
Country [289]
0
0
Korea, Republic of
Query!
State/province [289]
0
0
Busan
Query!
Country [290]
0
0
Korea, Republic of
Query!
State/province [290]
0
0
Daegu
Query!
Country [291]
0
0
Korea, Republic of
Query!
State/province [291]
0
0
Daejon
Query!
Country [292]
0
0
Korea, Republic of
Query!
State/province [292]
0
0
Goyang
Query!
Country [293]
0
0
Korea, Republic of
Query!
State/province [293]
0
0
Gwang Ju
Query!
Country [294]
0
0
Korea, Republic of
Query!
State/province [294]
0
0
Gyeonggi
Query!
Country [295]
0
0
Korea, Republic of
Query!
State/province [295]
0
0
Pusan
Query!
Country [296]
0
0
Korea, Republic of
Query!
State/province [296]
0
0
Scongnam-Si
Query!
Country [297]
0
0
Korea, Republic of
Query!
State/province [297]
0
0
Seoul
Query!
Country [298]
0
0
Korea, Republic of
Query!
State/province [298]
0
0
Suwon
Query!
Country [299]
0
0
Malaysia
Query!
State/province [299]
0
0
Kelantan
Query!
Country [300]
0
0
Malaysia
Query!
State/province [300]
0
0
Sarawak
Query!
Country [301]
0
0
Malaysia
Query!
State/province [301]
0
0
Selangor
Query!
Country [302]
0
0
Malaysia
Query!
State/province [302]
0
0
Kuala Lumpur
Query!
Country [303]
0
0
Mexico
Query!
State/province [303]
0
0
BAJA California
Query!
Country [304]
0
0
Mexico
Query!
State/province [304]
0
0
Distrito Federal
Query!
Country [305]
0
0
Mexico
Query!
State/province [305]
0
0
Jalisco
Query!
Country [306]
0
0
Mexico
Query!
State/province [306]
0
0
Michoacan
Query!
Country [307]
0
0
Mexico
Query!
State/province [307]
0
0
Nuevo LEON
Query!
Country [308]
0
0
Mexico
Query!
State/province [308]
0
0
Sinaloa
Query!
Country [309]
0
0
Mexico
Query!
State/province [309]
0
0
Veracruz
Query!
Country [310]
0
0
Mexico
Query!
State/province [310]
0
0
Puebla
Query!
Country [311]
0
0
Mexico
Query!
State/province [311]
0
0
Queretaro
Query!
Country [312]
0
0
Netherlands
Query!
State/province [312]
0
0
Breda
Query!
Country [313]
0
0
Netherlands
Query!
State/province [313]
0
0
Deventer
Query!
Country [314]
0
0
Netherlands
Query!
State/province [314]
0
0
Eindhoven
Query!
Country [315]
0
0
Netherlands
Query!
State/province [315]
0
0
Enschede
Query!
Country [316]
0
0
Netherlands
Query!
State/province [316]
0
0
Hardenberg
Query!
Country [317]
0
0
Netherlands
Query!
State/province [317]
0
0
Hilversum
Query!
Country [318]
0
0
Netherlands
Query!
State/province [318]
0
0
Nijmegen
Query!
Country [319]
0
0
Netherlands
Query!
State/province [319]
0
0
Oss
Query!
Country [320]
0
0
Netherlands
Query!
State/province [320]
0
0
Rotterdam
Query!
Country [321]
0
0
Netherlands
Query!
State/province [321]
0
0
S-Hertogenbosch
Query!
Country [322]
0
0
Netherlands
Query!
State/province [322]
0
0
Tiel
Query!
Country [323]
0
0
Netherlands
Query!
State/province [323]
0
0
Utrecht
Query!
Country [324]
0
0
Netherlands
Query!
State/province [324]
0
0
Velp
Query!
Country [325]
0
0
Norway
Query!
State/province [325]
0
0
Alesund
Query!
Country [326]
0
0
Norway
Query!
State/province [326]
0
0
Bergen
Query!
Country [327]
0
0
Norway
Query!
State/province [327]
0
0
Elverum
Query!
Country [328]
0
0
Norway
Query!
State/province [328]
0
0
Flekkefjord
Query!
Country [329]
0
0
Norway
Query!
State/province [329]
0
0
Nesttun
Query!
Country [330]
0
0
Norway
Query!
State/province [330]
0
0
Oslo
Query!
Country [331]
0
0
Norway
Query!
State/province [331]
0
0
Skien
Query!
Country [332]
0
0
Norway
Query!
State/province [332]
0
0
Stavanger
Query!
Country [333]
0
0
Norway
Query!
State/province [333]
0
0
Straume
Query!
Country [334]
0
0
Norway
Query!
State/province [334]
0
0
Tonsberg
Query!
Country [335]
0
0
Norway
Query!
State/province [335]
0
0
Tromso
Query!
Country [336]
0
0
Peru
Query!
State/province [336]
0
0
Callao
Query!
Country [337]
0
0
Peru
Query!
State/province [337]
0
0
Lambayeque
Query!
Country [338]
0
0
Peru
Query!
State/province [338]
0
0
Lima
Query!
Country [339]
0
0
Philippines
Query!
State/province [339]
0
0
Ilocos Norte
Query!
Country [340]
0
0
Philippines
Query!
State/province [340]
0
0
Manila
Query!
Country [341]
0
0
Philippines
Query!
State/province [341]
0
0
Naga City
Query!
Country [342]
0
0
Philippines
Query!
State/province [342]
0
0
Pasig City
Query!
Country [343]
0
0
Philippines
Query!
State/province [343]
0
0
Quezon City
Query!
Country [344]
0
0
Philippines
Query!
State/province [344]
0
0
Quezon
Query!
Country [345]
0
0
Philippines
Query!
State/province [345]
0
0
San Juan
Query!
Country [346]
0
0
Poland
Query!
State/province [346]
0
0
Gdynia
Query!
Country [347]
0
0
Poland
Query!
State/province [347]
0
0
Grodzisk Mazowiecki
Query!
Country [348]
0
0
Poland
Query!
State/province [348]
0
0
Inowroclaw
Query!
Country [349]
0
0
Poland
Query!
State/province [349]
0
0
Kielce
Query!
Country [350]
0
0
Poland
Query!
State/province [350]
0
0
Krakow
Query!
Country [351]
0
0
Poland
Query!
State/province [351]
0
0
Lodz
Query!
Country [352]
0
0
Poland
Query!
State/province [352]
0
0
Piotrkow Trybunalski
Query!
Country [353]
0
0
Poland
Query!
State/province [353]
0
0
Plock
Query!
Country [354]
0
0
Poland
Query!
State/province [354]
0
0
Plonsk
Query!
Country [355]
0
0
Poland
Query!
State/province [355]
0
0
Poznan
Query!
Country [356]
0
0
Poland
Query!
State/province [356]
0
0
Ruda Slaska
Query!
Country [357]
0
0
Poland
Query!
State/province [357]
0
0
Skierniewice
Query!
Country [358]
0
0
Poland
Query!
State/province [358]
0
0
Slupsk
Query!
Country [359]
0
0
Poland
Query!
State/province [359]
0
0
Torun
Query!
Country [360]
0
0
Poland
Query!
State/province [360]
0
0
Warszawa
Query!
Country [361]
0
0
Poland
Query!
State/province [361]
0
0
Wegrow
Query!
Country [362]
0
0
Puerto Rico
Query!
State/province [362]
0
0
Cayey
Query!
Country [363]
0
0
Puerto Rico
Query!
State/province [363]
0
0
Cidra
Query!
Country [364]
0
0
Puerto Rico
Query!
State/province [364]
0
0
Ponce
Query!
Country [365]
0
0
Romania
Query!
State/province [365]
0
0
Baia Mare
Query!
Country [366]
0
0
Romania
Query!
State/province [366]
0
0
Bucharest
Query!
Country [367]
0
0
Romania
Query!
State/province [367]
0
0
Cluj Napoca
Query!
Country [368]
0
0
Romania
Query!
State/province [368]
0
0
Iasi
Query!
Country [369]
0
0
Romania
Query!
State/province [369]
0
0
Oradea
Query!
Country [370]
0
0
Romania
Query!
State/province [370]
0
0
Sibiu
Query!
Country [371]
0
0
Romania
Query!
State/province [371]
0
0
Targu-Mures
Query!
Country [372]
0
0
Romania
Query!
State/province [372]
0
0
Timisoara
Query!
Country [373]
0
0
Romania
Query!
State/province [373]
0
0
Tirgu Mures
Query!
Country [374]
0
0
Russian Federation
Query!
State/province [374]
0
0
Chelyabinsk
Query!
Country [375]
0
0
Russian Federation
Query!
State/province [375]
0
0
Chita
Query!
Country [376]
0
0
Russian Federation
Query!
State/province [376]
0
0
Dzerzhinskiy
Query!
Country [377]
0
0
Russian Federation
Query!
State/province [377]
0
0
Kazan
Query!
Country [378]
0
0
Russian Federation
Query!
State/province [378]
0
0
Kemerovo
Query!
Country [379]
0
0
Russian Federation
Query!
State/province [379]
0
0
Kirovsk
Query!
Country [380]
0
0
Russian Federation
Query!
State/province [380]
0
0
Krasnodar
Query!
Country [381]
0
0
Russian Federation
Query!
State/province [381]
0
0
Moscow
Query!
Country [382]
0
0
Russian Federation
Query!
State/province [382]
0
0
Nizhni Novgorod
Query!
Country [383]
0
0
Russian Federation
Query!
State/province [383]
0
0
Novosibirsk
Query!
Country [384]
0
0
Russian Federation
Query!
State/province [384]
0
0
Odintsovo
Query!
Country [385]
0
0
Russian Federation
Query!
State/province [385]
0
0
Penza
Query!
Country [386]
0
0
Russian Federation
Query!
State/province [386]
0
0
Perm
Query!
Country [387]
0
0
Russian Federation
Query!
State/province [387]
0
0
Rostov-On-Don
Query!
Country [388]
0
0
Russian Federation
Query!
State/province [388]
0
0
Ryazan
Query!
Country [389]
0
0
Russian Federation
Query!
State/province [389]
0
0
Saint Petersburg
Query!
Country [390]
0
0
Russian Federation
Query!
State/province [390]
0
0
Saint-Petersburg
Query!
Country [391]
0
0
Russian Federation
Query!
State/province [391]
0
0
Samara
Query!
Country [392]
0
0
Russian Federation
Query!
State/province [392]
0
0
Saratov
Query!
Country [393]
0
0
Russian Federation
Query!
State/province [393]
0
0
St Petersburg
Query!
Country [394]
0
0
Russian Federation
Query!
State/province [394]
0
0
St-Petersburg
Query!
Country [395]
0
0
Russian Federation
Query!
State/province [395]
0
0
St. Petersburg
Query!
Country [396]
0
0
Russian Federation
Query!
State/province [396]
0
0
St.-Petersburg
Query!
Country [397]
0
0
Russian Federation
Query!
State/province [397]
0
0
St.Petersburg
Query!
Country [398]
0
0
Russian Federation
Query!
State/province [398]
0
0
Tomsk
Query!
Country [399]
0
0
Russian Federation
Query!
State/province [399]
0
0
Tumen
Query!
Country [400]
0
0
Russian Federation
Query!
State/province [400]
0
0
Tver
Query!
Country [401]
0
0
Russian Federation
Query!
State/province [401]
0
0
Voronezh
Query!
Country [402]
0
0
Russian Federation
Query!
State/province [402]
0
0
Yaroslavl
Query!
Country [403]
0
0
Russian Federation
Query!
State/province [403]
0
0
Zheleznodorozhniy
Query!
Country [404]
0
0
Russian Federation
Query!
State/province [404]
0
0
Zhukovsky
Query!
Country [405]
0
0
Singapore
Query!
State/province [405]
0
0
Singapore
Query!
Country [406]
0
0
South Africa
Query!
State/province [406]
0
0
Bloemfontein
Query!
Country [407]
0
0
South Africa
Query!
State/province [407]
0
0
Cape Town
Query!
Country [408]
0
0
South Africa
Query!
State/province [408]
0
0
Gauteng
Query!
Country [409]
0
0
South Africa
Query!
State/province [409]
0
0
KWA ZULU Natal
Query!
Country [410]
0
0
South Africa
Query!
State/province [410]
0
0
Western CAPE
Query!
Country [411]
0
0
Spain
Query!
State/province [411]
0
0
Alicante
Query!
Country [412]
0
0
Spain
Query!
State/province [412]
0
0
Almeria
Query!
Country [413]
0
0
Spain
Query!
State/province [413]
0
0
Galicia
Query!
Country [414]
0
0
Spain
Query!
State/province [414]
0
0
Albacete
Query!
Country [415]
0
0
Spain
Query!
State/province [415]
0
0
Barcelona
Query!
Country [416]
0
0
Spain
Query!
State/province [416]
0
0
Elda
Query!
Country [417]
0
0
Spain
Query!
State/province [417]
0
0
Figueres
Query!
Country [418]
0
0
Spain
Query!
State/province [418]
0
0
Gerona
Query!
Country [419]
0
0
Spain
Query!
State/province [419]
0
0
Las Palmas
Query!
Country [420]
0
0
Spain
Query!
State/province [420]
0
0
Madrid
Query!
Country [421]
0
0
Spain
Query!
State/province [421]
0
0
Palma De Mallorca
Query!
Country [422]
0
0
Spain
Query!
State/province [422]
0
0
San Sebastian De Los Reyes
Query!
Country [423]
0
0
Spain
Query!
State/province [423]
0
0
Tarragona
Query!
Country [424]
0
0
Spain
Query!
State/province [424]
0
0
Viladecans
Query!
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Sweden
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Goteberg
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Sweden
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Helsingborg
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Sweden
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Linkoping
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Sweden
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Lund
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Glasgow
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Funding & Sponsors
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Name
Bristol-Myers Squibb
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Summary
Brief summary
The trial seeks to determine if apixaban, an investigational anticoagulant (blood-thinner) is as effective as standard therapy (warfarin) in preventing stroke and systemic embolism in subjects with atrial fibrillation and risk factors for stroke.
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Trial website
https://clinicaltrials.gov/study/NCT00412984
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Trial related presentations / publications
Jamieson MJ, Byon W, Dettloff RW, Crawford M, Gargalovic PS, Merali SJ, Onorato J, Quintero AJ, Russ C. Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data. Am J Cardiovasc Drugs. 2022 Nov;22(6):615-631. doi: 10.1007/s40256-022-00524-x. Epub 2022 May 16. Pol T, Hijazi Z, Lindback J, Oldgren J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Yusuf S, Siegbahn A, Wallentin L. Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation. Cardiovasc Res. 2022 Jul 20;118(9):2112-2123. doi: 10.1093/cvr/cvab262. Pol T, Hijazi Z, Lindback J, Alexander JH, Bahit MC, De Caterina R, Eikelboom JW, Ezekowitz MD, Gersh BJ, Granger CB, Hylek EM, Lopes R, Siegbahn A, Wallentin L. Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas. Open Heart. 2021 Mar;8(1):e001471. doi: 10.1136/openhrt-2020-001471. Hijazi Z, Wallentin L, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Pol T, Yusuf S, Oldgren J, Siegbahn A. Screening of Multiple Biomarkers Associated With Ischemic Stroke in Atrial Fibrillation. J Am Heart Assoc. 2020 Dec 15;9(24):e018984. doi: 10.1161/JAHA.120.018984. Epub 2020 Dec 9. Wallentin L, Lindback J, Eriksson N, Hijazi Z, Eikelboom JW, Ezekowitz MD, Granger CB, Lopes RD, Yusuf S, Oldgren J, Siegbahn A. Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation. Eur Heart J. 2020 Nov 1;41(41):4037-4046. doi: 10.1093/eurheartj/ehaa697. Hijazi Z, Granger CB, Hohnloser SH, Westerbergh J, Lindback J, Alexander JH, Keltai M, Parkhomenko A, Lopez-Sendon JL, Lopes RD, Siegbahn A, Wallentin L. Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation. J Am Heart Assoc. 2020 Sep 15;9(18):e017155. doi: 10.1161/JAHA.120.017155. Epub 2020 Aug 31. Zeitouni M, Giczewska A, Alexander JH. Reply: Specifics of Dose Modification in ARISTOTLE. J Am Coll Cardiol. 2020 Jul 7;76(1):128-129. doi: 10.1016/j.jacc.2020.05.013. No abstract available. Rosjo H, Hijazi Z, Omland T, Westerbergh J, Lyngbakken MN, Alexander JH, Gersh BJ, Granger CB, Hylek EM, Lopes RD, Siegbahn A, Wallentin L. Cardiac troponin is associated with cardiac outcomes in men and women with atrial fibrillation, insights from the ARISTOTLE trial. J Intern Med. 2020 Aug;288(2):248-259. doi: 10.1111/joim.13072. Epub 2020 May 18. Zeitouni M, Giczewska A, Lopes RD, Wojdyla DM, Christersson C, Siegbahn A, De Caterina R, Steg PG, Granger CB, Wallentin L, Alexander JH; ARISTOTLE Investigators. Clinical and Pharmacological Effects of Apixaban Dose Adjustment in the ARISTOTLE Trial. J Am Coll Cardiol. 2020 Mar 17;75(10):1145-1155. doi: 10.1016/j.jacc.2019.12.060. Stanifer JW, Pokorney SD, Chertow GM, Hohnloser SH, Wojdyla DM, Garonzik S, Byon W, Hijazi Z, Lopes RD, Alexander JH, Wallentin L, Granger CB. Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease. Circulation. 2020 Apr 28;141(17):1384-1392. doi: 10.1161/CIRCULATIONAHA.119.044059. Epub 2020 Mar 12. Garcia DA, Fisher DA, Mulder H, Wruck L, De Caterina R, Halvorsen S, Granger CB, Held C, Wallentin L, Alexander JH, Lopes RD. Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Am Heart J. 2020 Mar;221:1-8. doi: 10.1016/j.ahj.2019.10.013. Epub 2019 Oct 31. Dalgaard F, Mulder H, Wojdyla DM, Lopes RD, Held C, Alexander JH, De Caterina R, Washam JB, Hylek EM, Garcia DA, Gersh BJ, Wallentin L, Granger CB, Al-Khatib SM. Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial. Circulation. 2020 Jan 7;141(1):10-20. doi: 10.1161/CIRCULATIONAHA.119.041296. Epub 2019 Nov 21. Goldstein SA, Green J, Huber K, Wojdyla DM, Lopes RD, Alexander JH, Vinereanu D, Wallentin L, Granger CB, Al-Khatib SM. Characteristics and Outcomes of Atrial Fibrillation in Patients With Thyroid Disease (from the ARISTOTLE Trial). Am J Cardiol. 2019 Nov 1;124(9):1406-1412. doi: 10.1016/j.amjcard.2019.07.046. Epub 2019 Aug 7. Guimaraes PO, Pokorney SD, Lopes RD, Wojdyla DM, Gersh BJ, Giczewska A, Carnicelli A, Lewis BS, Hanna M, Wallentin L, Vinereanu D, Alexander JH, Granger CB. Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial. Clin Cardiol. 2019 May;42(5):568-571. doi: 10.1002/clc.23178. Epub 2019 Apr 9. Washam JB, Hohnloser SH, Lopes RD, Wojdyla DM, Vinereanu D, Alexander JH, Gersh BJ, Hanna M, Horowitz J, Hylek EM, Xavier D, Verheugt FWA, Wallentin L, Granger CB; ARISTOTLE Committees and Investigators. Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial. J Thromb Thrombolysis. 2019 Apr;47(3):345-352. doi: 10.1007/s11239-019-01823-y. Hohnloser SH, Fudim M, Alexander JH, Wojdyla DM, Ezekowitz JA, Hanna M, Atar D, Hijazi Z, Bahit MC, Al-Khatib SM, Lopez-Sendon JL, Wallentin L, Granger CB, Lopes RD. Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight. Circulation. 2019 May 14;139(20):2292-2300. doi: 10.1161/CIRCULATIONAHA.118.037955. Alexander KP, Brouwer MA, Mulder H, Vinereanu D, Lopes RD, Proietti M, Al-Khatib SM, Hijazi Z, Halvorsen S, Hylek EM, Verheugt FWA, Alexander JH, Wallentin L, Granger CB; ARISTOTLE Investigators. Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial. Am Heart J. 2019 Feb;208:123-131. doi: 10.1016/j.ahj.2018.09.017. Epub 2018 Nov 22. Sandhu RK, Ezekowitz JA, Hijazi Z, Westerbergh J, Aulin J, Alexander JH, Granger CB, Halvorsen S, Hanna MS, Lopes RD, Siegbahn A, Wallentin L. Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial. Open Heart. 2018 Nov 1;5(2):e000908. doi: 10.1136/openhrt-2018-000908. eCollection 2018. Christersson C, Wallentin L, Andersson U, Alexander JH, Alings M, De Caterina R, Gersh BJ, Granger CB, Halvorsen S, Hanna M, Huber K, Hylek EM, Lopes RD, Oh BH, Siegbahn A. Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation. Heart. 2019 Feb;105(3):235-242. doi: 10.1136/heartjnl-2018-313351. Epub 2018 Sep 12. Horowitz JD, De Caterina R, Heresztyn T, Alexander JH, Andersson U, Lopes RD, Steg PG, Hylek EM, Mohan P, Hanna M, Jansky P, Granger CB, Wallentin L; ARISTOTLE Investigators. Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy. J Am Coll Cardiol. 2018 Aug 14;72(7):721-733. doi: 10.1016/j.jacc.2018.05.058. Sharma A, Hijazi Z, Andersson U, Al-Khatib SM, Lopes RD, Alexander JH, Held C, Hylek EM, Leonardi S, Hanna M, Ezekowitz JA, Siegbahn A, Granger CB, Wallentin L. Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. Circulation. 2018 Oct 16;138(16):1666-1676. doi: 10.1161/CIRCULATIONAHA.118.034125. Kopin D, Jones WS, Sherwood MW, Wojdyla DM, Wallentin L, Lewis BS, Verheugt FWA, Vinereanu D, Bahit MC, Halvorsen S, Huber K, Parkhomenko A, Granger CB, Lopes RD, Alexander JH. Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial. Am Heart J. 2018 Mar;197:133-141. doi: 10.1016/j.ahj.2017.11.005. Epub 2017 Nov 10. Pol T, Held C, Westerbergh J, Lindback J, Alexander JH, Alings M, Erol C, Goto S, Halvorsen S, Huber K, Hanna M, Lopes RD, Ruzyllo W, Granger CB, Hijazi Z. Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. J Am Heart Assoc. 2018 Feb 1;7(3):e007444. doi: 10.1161/JAHA.117.007444. Goto S, Merrill P, Wallentin L, Wojdyla DM, Hanna M, Avezum A, Easton JD, Harjola VP, Huber K, Lewis BS, Parkhomenko A, Zhu J, Granger CB, Lopes RD, Alexander JH. Antithrombotic therapy use and clinical outcomes following thrombo-embolic events in patients with atrial fibrillation: insights from ARISTOTLE. Eur Heart J Cardiovasc Pharmacother. 2018 Apr 1;4(2):75-81. doi: 10.1093/ehjcvp/pvy002. Vinereanu D, Wang A, Mulder H, Lopes RD, Jansky P, Lewis BS, Gersh BJ, Avezum A, Hanna M, Held C, Wallentin L, Granger CB, Alexander JH. Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease. Heart. 2018 Aug;104(15):1292-1299. doi: 10.1136/heartjnl-2017-312272. Epub 2018 Jan 19. Rao MP, Vinereanu D, Wojdyla DM, Alexander JH, Atar D, Hylek EM, Hanna M, Wallentin L, Lopes RD, Gersh BJ, Granger CB; Apixaban for Reduction in Stroke Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators. Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial. Am J Med. 2018 Mar;131(3):269-275.e2. doi: 10.1016/j.amjmed.2017.10.036. Epub 2017 Nov 6. Vinereanu D, Lopes RD, Mulder H, Gersh BJ, Hanna M, de Barros E Silva PGM, Atar D, Wallentin L, Granger CB, Alexander JH; ARISTOTLE Investigators. Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin. Stroke. 2017 Dec;48(12):3266-3273. doi: 10.1161/STROKEAHA.117.017574. Epub 2017 Oct 31. Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, Yusuf S, Granger CB, Siegbahn A, Wallentin L; ARISTOTLE and RE-LY Investigators. A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. Eur Heart J. 2018 Feb 7;39(6):477-485. doi: 10.1093/eurheartj/ehx584. Hijazi Z, Lindahl B, Oldgren J, Andersson U, Lindback J, Granger CB, Alexander JH, Gersh BJ, Hanna M, Harjola VP, Hylek EM, Lopes RD, Siegbahn A, Wallentin L. Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time. J Am Heart Assoc. 2017 Jun 23;6(6):e004851. doi: 10.1161/JAHA.116.004851. Lopes RD, Guimaraes PO, Kolls BJ, Wojdyla DM, Bushnell CD, Hanna M, Easton JD, Thomas L, Wallentin L, Al-Khatib SM, Held C, Gabriel Melo de Barros E Silva P, Alexander JH, Granger CB, Diener HC. Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Blood. 2017 Jun 1;129(22):2980-2987. doi: 10.1182/blood-2016-08-731638. Epub 2017 Mar 29. Cowper PA, Sheng S, Lopes RD, Anstrom KJ, Stafford JA, Davidson-Ray L, Al-Khatib SM, Ansell J, Dorian P, Husted S, McMurray JJV, Steg PG, Alexander JH, Wallentin L, Granger CB, Mark DB. Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2017 May 1;2(5):525-534. doi: 10.1001/jamacardio.2017.0065. Hu PT, Lopes RD, Stevens SR, Wallentin L, Thomas L, Alexander JH, Hanna M, Lewis BS, Verheugt FW, Granger CB, Jones WS. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial. J Am Heart Assoc. 2017 Jan 17;6(1):e004699. doi: 10.1161/JAHA.116.004699. Bahit MC, Lopes RD, Wojdyla DM, Held C, Hanna M, Vinereanu D, Hylek EM, Verheugt F, Goto S, Alexander JH, Wallentin L, Granger CB. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. Heart. 2017 Apr;103(8):623-628. doi: 10.1136/heartjnl-2016-309901. Epub 2016 Oct 24. Oldgren J, Hijazi Z, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Granger CB, Hylek EM, Lopes RD, Siegbahn A, Yusuf S, Wallentin L; RE-LY and ARISTOTLE Investigators. Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation. Circulation. 2016 Nov 29;134(22):1697-1707. doi: 10.1161/CIRCULATIONAHA.116.022802. Epub 2016 Aug 28. Alexander JH, Andersson U, Lopes RD, Hijazi Z, Hohnloser SH, Ezekowitz JA, Halvorsen S, Hanna M, Commerford P, Ruzyllo W, Huber K, Al-Khatib SM, Granger CB, Wallentin L; Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) Investigators. Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 Sep 1;1(6):673-81. doi: 10.1001/jamacardio.2016.1829. Hijazi Z, Hohnloser SH, Andersson U, Alexander JH, Hanna M, Keltai M, Parkhomenko A, Lopez-Sendon JL, Lopes RD, Siegbahn A, Granger CB, Wallentin L. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2016 Jul 1;1(4):451-60. doi: 10.1001/jamacardio.2016.1170. Jaspers Focks J, Brouwer MA, Wojdyla DM, Thomas L, Lopes RD, Washam JB, Lanas F, Xavier D, Husted S, Wallentin L, Alexander JH, Granger CB, Verheugt FW. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016 Jun 15;353:i2868. doi: 10.1136/bmj.i2868. Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, Siegbahn A, Yusuf S, Granger CB, Wallentin L; ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016 Jun 4;387(10035):2302-2311. doi: 10.1016/S0140-6736(16)00741-8. Epub 2016 Apr 4. Hijazi Z, Lindback J, Alexander JH, Hanna M, Held C, Hylek EM, Lopes RD, Oldgren J, Siegbahn A, Stewart RA, White HD, Granger CB, Wallentin L; ARISTOTLE and STABILITY Investigators. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J. 2016 May 21;37(20):1582-90. doi: 10.1093/eurheartj/ehw054. Epub 2016 Feb 25. Hijazi Z, Aulin J, Andersson U, Alexander JH, Gersh B, Granger CB, Hanna M, Horowitz J, Hylek EM, Lopes RD, Siegbahn A, Wallentin L; ARISTOTLE Investigators. Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. 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