A Phase III Study of Apixaban in Patients With Atrial Fibrillation

Overview[ - collapse ][ - ]

Purpose The purpose of this clinical research study is to determine whether apixaban is more effective than acetylsalicylic acid in the prevention of strokes associated with patients with atrial fibrillation. The safety of this treatment will also be studied.
ConditionAtrial Fibrillation
InterventionDrug: Apixaban
Drug: Acetylsalicylic acid
PhasePhase 3
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT00496769
First ReceivedJuly 2, 2007
Last UpdatedOctober 22, 2013
Last verifiedOctober 2013

Tracking Information[ + expand ][ + ]

First Received DateJuly 2, 2007
Last Updated DateOctober 22, 2013
Start DateSeptember 2007
Estimated Primary Completion DateDecember 2013
Current Primary Outcome Measures
  • Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period [Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)] [Designated as safety issue: No]Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)
  • Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period [Time Frame: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)] [Designated as safety issue: Yes]Event rate=percent of participants with an event divided by the total participants in the arm.
Current Secondary Outcome Measures
  • Event Rates of Major Vascular Events (Stroke/Systemic Embolism, Myocardial Infarction, Death) in the Intended-treatment Period [Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)] [Designated as safety issue: No]Event rate=percent of participants with an event divided by the total participants in the arm.
  • Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period [Time Frame: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010] [Designated as safety issue: No]Event rate=percent of participants with an event divided by the total participants in the arm.
  • Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome [Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug] [Designated as safety issue: Yes]AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
  • Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality [Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug] [Designated as safety issue: Yes]BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL>2 or value ≤8; hematocrit(%), low: <0.75*BL; erythrocytes (*10^6 cells/μL), low: <0.75*BL; platelet count (*10^9 cells/L),low: <100*10^9 cells/L; leukocytes (*10^3 cells/μL), low if <0.8*BL and BLULN or <0.75*LLN when BL is missing or LLN ≤BL≤ ULN, high if >1.2*BL and BL>ULN or >ULN when BL and BL1.25*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: <1.0*10^3 cells/μL; eosinophils (absolute), high: >0.750*10^3 cells/μL; basophils (absolute), high: >0.4*10^3 cells/μL; monocytes (absolute), high: 2*10^3 cells/μL; lymphocytes (absolute), low if <0.75*10^3 cells/μL, high if >7.50*10^3 cells/μL; ALP (U/L), high: 2*ULN; AST (U/L), high: 3*ULN; AST (U/L), high: 3*ULN; bilirubin, total (mg/dL), high: >2*ULN; bilirubin, direct (mg/dL), high: 1.5*ULN; BUN (mg/dL), high:>2*ULN; creatinine (mg/dL), high: >1.5*ULN.
  • Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) [Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug] [Designated as safety issue: Yes]LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if <0.95*BL and BLULN or <0.95*LLN when BL missing or LLN ≤BL≤ULN, high if >1.05*BL and BL>ULN or >ULN and BL1.05*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if <0.90*BL and BLULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL and BL>ULN or>ULN and BL1.10*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if <0.90*BL and BLULN or <0.90*LLN if BL missing or LLN≤BL ≤ULN, high if >1.10*BL and BL>ULN or >ULN and BL1.10* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if <0.75*BL and BLULN or <0.80*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL and BL>ULN or >ULN if BL1.20*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if <0.75*BL when BLULN or <0.75*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL when BL>ULN or >ULN
  • Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) [Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug] [Designated as safety issue: Yes]ULN=upper limit of normal; LLN=lower limit ofnormal; BL=baseline. Creatine kinase (U/L), high:>5*ULN; protein, total(g/L):low if <0.90*BL when BLULN or <0.90*LLN when BL is missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN when BL1.10*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if <0.90*BL if BLULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN if BL1.10*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if <0.8*BL if BLULN or <0.8*LLN when BL missing or LLN≤BL≤ULN, high if >2*BL when BL>ULN or >ULN when BL1.5*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: >2*BL and BL>ULN or>1.5*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2.
  • Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death [Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)] [Designated as safety issue: No]Event rate=percent of participants with an event divided by the total participants in the arm.

Descriptive Information[ + expand ][ + ]

Brief TitleA Phase III Study of Apixaban in Patients With Atrial Fibrillation
Official TitleApixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment: A Randomized Double-blind Trial
Brief Summary
The purpose of this clinical research study is to determine whether apixaban is more
effective than acetylsalicylic acid in the prevention of strokes associated with patients
with atrial fibrillation. The safety of this treatment will also be studied.
Detailed Description
An optional Long-term Open-label Extension Phase of treatment with apixaban will be provided
for qualifying participants following the conclusion of the double-blind phase
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
ConditionAtrial Fibrillation
InterventionDrug: Apixaban
Tablets, oral, 5 mg (2.5 mg in patients meeting any 2 of the following criteria: 80 years of age and older, weight of 60 kilograms or less, and a serum creatinine level of 1.5 mg/dL or higher), twice daily, up to 156 weeks
Other Names:
BMS-562247Drug: Acetylsalicylic acid
Tablets, oral, 81-324 mg, once daily, up to 156 weeks
Study Arm (s)
  • Experimental: Apixaban
  • Active Comparator: Acetylasalicylic acid

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment6421
Estimated Completion DateDecember 2013
Estimated Primary Completion DateNovember 2010
Eligibility Criteria
Key Inclusion Criteria:

- Male and female

- Age of 50 years or older

- Permanent, paroxysmal, or persistent atrial fibrillation (at screening or within 6
months prior to enrollment) documented by 12-lead electrocardiogram)

- At least 1 of the following risk factors for stroke:

- Prior stroke or transient ischemic attack

- Age of 75 years or older

- Arterial hypertension on treatment

- Diabetes mellitus

- Heart failure (New York Health Authority Class 2 or greater at time of
enrollment)

- Left ventricular ejection fraction of 35% or less, documented within 6 months of
enrollment

- Peripheral arterial disease (previous arterial revascularization, limb or foot
amputation, or current intermittent claudication with ankle-arm systolic blood
pressure ratio <0.9)

- Not currently receiving vitamin K antagonist therapy for 1 of the following reasons:

- Previous vitamin K antagonist therapy demonstrated as unsuitable and
discontinued

- Vitamin K antagonist therapy not previously used but expected unsuitable

Key Exclusion Criteria:

- Women who are pregnant or breast feeding

- Women of child bearing potential who are unwilling to meet the study requirements for
pregnancy testing or are unwilling or unable to use an acceptable method to avoid
pregnancy

- Atrial fibrillation due to reversible causes, such as thyrotoxicosis or pericarditis

- Valvular disease requiring surgery

- Planned ablation procedure for atrial fibrillation to be performed within 3 months

- Conditions other than atrial fibrillation that require chronic anticoagulation (such
as, prosthetic mechanical heart valve, venous thromboembolism)

- Patients with serious bleeding in the last 6 months or at high risk for bleeding,
including but not limited to those with:

- Active peptic ulcer disease

- Platelet count <100,000/mm^3 or hemoglobin <10g/dL

- Recent stroke (within 10 days)

- Documented hemorrhagic tendencies or blood dyscrasias

- Current alcohol or drug abuse or psychosocial reasons that make study participation
impractical

- Severe comorbid condition with life expectancy <1 year

- Severe renal insufficiency; any patient with a serum creatinine level >2.5 mg/dL or a
calculated creatinine clearance <25 mL/min is excluded

- Alanine transaminase or aspartate aminotransferase levels >2 times upper limit of
normal (ULN) or a total bilirubin level >1.5 times ULN (unless an alternative
causative factor [such as Gilbert's syndrome] is identified)

- Allergy or adverse reaction to acetylsalicylic acid

- Required treatment with a thienopyridine (clopidogrel or ticlopidine)

- Prisoners or participants who are compulsory detained (involuntarily incarcerated)

- Use of an investigational drug or device within the past 30 days or prior
randomization into an apixaban clinical study

- Patients who are compulsorily detained for treatment for a psychiatric or physical
illness
GenderBoth
Ages50 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, India, Indonesia, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Norway, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00496769
Other Study ID NumbersCV185-048
Has Data Monitoring CommitteeYes
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsPfizer
Investigators Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification DateOctober 2013

Locations[ + expand ][ + ]

Mobile Heart Specialists, Pc
Mobile, Alabama, United States, 36608
Southwest Heart
Tucscon, Arizona, United States, 85710
Cardiology Consultants Of Orange County Med. Group Inc
Anaheim, California, United States, 92801
Kaiser Permanente Medical Center, West Los Angeles
Los Angeles, California, United States, 90034
Desert Med Grp Inc, Dba Desert Oasis Healthcare Med Group
Palm Springs, California, United States, 92262
Yogesh K. Paliwal Md
Pomona, California, United States, 91767
San Diego Managed Care Group
Poway, California, United States, 92064
University Of California San Diego
San Diego, California, United States, 92103
Santa Rosa Cardiology Medical Group, Inc.
Santa Rosa, California, United States, 95405
North County Internal Medicine
Vista, California, United States, 92083
Cardiology Associates Of New Haven,Pc
Guilford, Connecticut, United States, 06437
Stamford Therapeutics Consortium
Stamford, Connecticut, United States, 06905
Bay Pines Va Healthcare System
Bay Pines, Florida, United States, 33744
Research Alliance, Inc.
Clearwater, Florida, United States, 33756
The Heart & Vascular Institute Of Florida
Clearwater, Florida, United States, 33756
Kim A. Klancke, Md
Daytona Beach, Florida, United States, 32114
The Heart Group Of Lee Memorial Health System
Fort Myers, Florida, United States, 33908
St. Vincent'S Ambulatory Care, Inc.
Jacksonville, Florida, United States, 32204
Jacksonville Heart Center, P.A.
Jacksonville Beach, Florida, United States, 32250
Michael F. Lesser, Md, Facc Osler Medical Inc.
Melbourne, Florida, United States, 32901
Cardiovascular Center Of Sarasota
Sarasota, Florida, United States, 34239
Integrated Care Llc D/B/A Cardiovascular Consultants Of S Fl
Tamarac, Florida, United States, 33321
Southeast Regional Research Group
Columbus, Georgia, United States, 31904
Southeast Regional Research Group
Savannah, Georgia, United States, 31406
Fox Valley Clinical Research Center, Llc
Aurora, Illinois, United States, 60504
North Chicago Va Medical Center
North Chicago, Illinois, United States, 60064
St Francis Medical Group - Indiana Heart Physicians
Indianapolis, Indiana, United States, 46237
St. Vincent Medical Group, Inc.
Indianapolis, Indiana, United States, 46290
Hutchinson Clinic, Pa
Hutchinson, Kansas, United States, 67502
Dr. Jeffrey Chen
Lafayette, Louisiana, United States, 70506
Peninsula Cardiology Associates, P.A.
Salisbury, Maryland, United States, 21804
Pentucket Medical Associates
Haverhill, Massachusetts, United States, 01830
Great Lakes Heart Center Of Alpena
Alpena, Michigan, United States, 49707
Henry Ford Hospital K-15
Detroit, Michigan, United States, 48202
Michigan Heart And Vascular Specialists
Petoskey, Michigan, United States, 49770
Academic Cardiology Associates
Rochester Hills, Michigan, United States, 48307
Tupelo Neurology Clinic, Pa
Tupelo, Mississippi, United States, 38801
University Of Missouri
Columbia, Missouri, United States, 65212
Missouri Cardiovascular Specialists
Columbia, Missouri, United States, 65201
Glacier View Cardiology, Pc
Kalispell, Montana, United States, 59901
Hunterdon Cardiovascular Associates
Flemington, New Jersey, United States, 08822
Capital Cardiology Associates
Albany, New York, United States, 12211
Hudson Valley Cardiology Group, P.C.
Cortlandt Manor, New York, United States, 10567
Long Island Heart Associates
Mineola, New York, United States, 11501
Dr William Kufs
Saratoga Springs, New York, United States, 12866
Capital Cardiology Associates
Troy, New York, United States, 12180
Terry V. Arnold, Md
Lexington, North Carolina, United States, 27293
Pinehurst Medical Clinic, Inc
Pinehurst, North Carolina, United States, 28374
Sanford Cardiology
Sanford, North Carolina, United States, 27330
Ira R. Friedlander, M.D.
Canton, Ohio, United States, 44710
Davis Heart & Lung Research Institute
Columbus, Ohio, United States, 43210
South Oklahoma Heart Research
Oklahoma City, Oklahoma, United States, 73135
Integris Cardiovascular Physicians
Oklahoma City, Oklahoma, United States, 73112
Oregon Medical Group Clinical Research
Eugene, Oregon, United States, 97401
Hillsboro Cardiology Pc
Hillsboro, Oregon, United States, 97123
The Portland Clinic, Llp
Portland, Oregon, United States, 97205
Comprehensive Cardiology Consultants
Langhorne, Pennsylvania, United States, 19047
Buxmont Cardiology Associates
Sellersville, Pennsylvania, United States, 18960
West Chester Cardiology
West Chester, Pennsylvania, United States, 19380
Cardiology Consultants Of Philadelphia
Yardley, Pennsylvania, United States, 19067
Lowcountry Medical Group
Beaufort, South Carolina, United States, 29906
Medical University Of South Carolina
Charleston, South Carolina, United States, 29425
Internal Medicine Of Greer
Greer, South Carolina, United States, 29650
Knoxville Heart Group
Knoxville, Tennessee, United States, 37916
Sentara York Clinical Research
Norfolk, Virginia, United States, 23510
Roanoke Heart Institute, Plc
Roanoke, Virginia, United States, 24014
Salem Veterans Administration Medical Center
Salem, Virginia, United States, 24153
Walla Walla Clinic
Walla Walla, Washington, United States, 99362
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Local Institution
Adrogue, Buenos Aires, Argentina, B1846DSK
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Autonoma Buenos Aires, Buenos Aires, Argentina, C1119ACN
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Bahia Blanca, Buenos Aires, Argentina, B8000FTD
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Coronel Suarez, Buenos Aires, Argentina, B7540GHD
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Haedo, Buenos Aires, Argentina, B1706AJO
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La Plata, Buenos Aires, Argentina, B1902COS
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La Plata, Buenos Aires, Argentina, B1900AXI
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Merlo, Buenos Aires, Argentina, B1722COV
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Ramos Mejia, Buenos Aires, Argentina, B1704ETD
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San Francisco, Cordoba, Argentina, X2400MHC
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San Salvador De Jujuy, Jujuy, Argentina, Y4600ABF
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Zarate, Provincia Buenos Aires, Argentina, B2800DGH
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Rosario, Santa Fe, Argentina, S2000CVD
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Rosario, Santa Fe, Argentina, S2001ODA
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Rosario, Santa Fe, Argentina, S2000CVB
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San Miguel De Tucuman, Tucuman, Argentina, T4000ICL
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San Miguel De Tucuman, Tucuman, Argentina, T4000JCU
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Buenos Aires, Argentina, C1221ADC
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Cordoba, Argentina, X5016KEH
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Cordoba, Argentina, X5000EVQ
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Cordoba, Argentina, X5002AOQ
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Cordoba, Argentina, X5000AAX
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Cordoba, Argentina, X5009BSN
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Cordoba, Argentina, X5000EPU
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Corrientes, Argentina, W3400AMZ
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Mar Del Plata, Argentina, B7600FZN
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Salta, Argentina, A4406CLA
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Santa Fe, Argentina, S3000FWO
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Coffs Harbour, New South Wales, Australia, 2450
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Concord, New South Wales, Australia, 2139
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Gosford, New South Wales, Australia, 2250
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Kingswood, New South Wales, Australia, 2747
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Auchenflower, Queensland, Australia, 4066
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Kippa Ring, Queensland, Australia, 4021
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Milton, Queensland, Australia, 4064
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Woolloongabba, Queensland, Australia, 4102
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Geelong, Victoria, Australia, 3220
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Joondalup, Western Australia, Australia, 6027
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Graz, Austria, 8036
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Linz, Austria, 4020
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Oberpullendorf, Austria, 7350
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Salzburg, Austria, 5020
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Aalst, Belgium, 9300
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Brasschaat, Belgium, 2930
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Brussel, Belgium, 1090
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Bruxelles, Belgium, 1070
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De Pinte, Belgium, 9840
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Genk, Belgium, 3600
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Huy, Belgium, 4500
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Roeselare, Belgium, 8800
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Turnhout, Belgium, 2300
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Salvador, Bahia, Brazil, 41810-010
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Salvador, Bahia, Brazil, 40144-000
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Belo Horizonte, Minas Gerais, Brazil, 30150-221
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Uberaba, Minas Gerais, Brazil, 38010
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Uberaba, Minas Gerais, Brazil, 38025
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Campina Grande Do Sul, Parana, Brazil, 83430-000
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Curitiba, Parana, Brazil, 80010
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Curitiba, Parana, Brazil, 80730-150
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Maringa, Parana, Brazil, 87015-290
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Belem, Para, Brazil, 66120-330
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Natal, Rio Grande Do Norte, Brazil, 59020-100
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Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
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Porto Alegre, Rio Grande Do Sul, Brazil, 90035
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Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
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Porto Alegre, Rio Grande Do Sul, Brazil, 90620-001
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Porto Alegre, Rio Grande Do Sul, Brazil, 90110-270
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Porto Alegre, Rio Grande do Sul, Brazil, 90610
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Blumenau, Santa Catarina, Brazil, 89010-500
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Sao Jose, Santa Catarina, Brazil, 88103-460
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Botucatu, Sao Paulo, Brazil, 18600-400
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Campinas, Sao Paulo, Brazil, 13059-740
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Marilia, Sao Paulo, Brazil, 17515-000
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Marilia, Sao Paulo, Brazil, 17515
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Marilia, Sao Paulo, Brazil, 17519-030
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San Jose- Do Rio Preto, Sao Paulo, Brazil, 15015-210
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Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15090
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Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15025-130
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Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15015-750
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Rio De Janeiro, Brazil, 20551-030
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Sao Paulo, Brazil, 04012-180
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Sao Paulo, Brazil, 05403
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Sao Paulo, Brazil, 04038
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Sao Paulo, Brazil, 04012-909
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Sao Paulo, Brazil, 05403-010
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New Westminster, British Columbia, Canada, V3L 3W4
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Winnipeg, Manitoba, Canada, R2V 4W3
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Brampton, Ontario, Canada, L6W 2X7
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Burlington, Ontario, Canada, L7M 4Y1
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Cambridge, Ontario, Canada, N1R 6V6
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Cambridge, Ontario, Canada, N1R 7R1
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Grimsby, Ontario, Canada, L3M 1P3
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Hamilton, Ontario, Canada, L8L 2X2
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Hamilton, Ontario, Canada, L8M 1K7
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Oshawa, Ontario, Canada, L1J 2J9
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Oshawa, Ontario, Canada, L1H 1B9
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Ottawa, Ontario, Canada, K1Y 4W7
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Sarnia, Ontario, Canada, N7T 4X3
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Sudbury, Ontario, Canada, P3E 2N8
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Sudbury, Ontario, Canada, P3C 5K7
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Toronto, Ontario, Canada, M5B 1W8
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Toronto, Ontario, Canada, M4N 3M5
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Weston, Ontario, Canada, M9N 1W4
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Greenfield Park, Quebec, Canada, J4V 2G8
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Montreal, Quebec, Canada, H2W 1T8
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Montreal, Quebec, Canada, H1T 1C8
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Montreal, Quebec, Canada, H2K 4L5
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St. Georges Beauce, Quebec, Canada, G5Y 4W1
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St. Jerome, Quebec, Canada, J7Z 5T3
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St. Lambert, Quebec, Canada, J4P 2H4
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Terrebonne, Quebec, Canada, J6V 2H2
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Westmount, Quebec, Canada, H3Z 2M6
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Saskatoon, Saskatchewan, Canada, S7L 2Y7
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Quebec, Canada, G1J 1Z6
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Temuco, Araucania, Chile, 4781173
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Victoria, Araucania, Chile, 4720000
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Osorno, Los Lagos, Chile, 5311089
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Valdivia, Los Rios, Chile, 5111847
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Santiago, Metropolitana, Chile, 8900085
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Santiago, Metropolitana, Chile, 7600448
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Santiago, Metropolitana, Chile, 8360160
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Santiago, Metropolitana, Chile, 8330074
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Santiago, Metropolitana, Chile, 7500520
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Vina Del Mar, Valparaiso, Chile, 2570017
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Beijing, Beijing, China, 100853
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Beijing, Beijing, China, 100037
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Beijing, Beijing, China, 100020
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Beijing, Beijing, China, 100029
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Beijing, Beijing, China, 100038
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Beijing, Beijing, China, 100088
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Guangzhou, Guangdong, China, 510180
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Shijiazhuang, Hebei, China, 50082
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Wuhan, Hubei, China, 430060
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Suzhou, Jiangsu, China, 215006
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Dalian, Liaoning, China, 116033
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Shenyang, Liaoning, China, 110001
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Qingdao, Shandong, China, 266071
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Shanghai, Shanghai, China, 200025
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Shanghai, Shanghai, China, 200433
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Chengdu, Sichuan, China, 610041
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Medellin, Antioquia, Colombia
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Barranquilla, Atlantico, Colombia, -----
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Bucaramanga, Santander, Colombia
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Cali, Valle Del Cauca, Colombia
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Bogota, Colombia
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Brno, Czech Republic, 656 91
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Havirov - Mesto, Czech Republic, 736 01
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Jindrichuv Hradec, Czech Republic, 377 38
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Kladno, Czech Republic, 272 59
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Kromeriz, Czech Republic, 767 55
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Mestec Kralove, Czech Republic, 289 03
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Ostrava, Czech Republic, 702 00
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Pisek, Czech Republic, 397 01
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Praha 1, Czech Republic, 110 00
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Praha 2, Czech Republic, 128 08
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Praha 5, Czech Republic, 150 00
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Prelouc, Czech Republic, 535 01
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Pribram, Czech Republic, 261 26
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Slany, Czech Republic, 274 01
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Usti Nad Orlici, Czech Republic, 562 18
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Arhus C, Denmark, 8000
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Esbjerg, Denmark, 6700
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Frederiksberg, Denmark, 2000
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Espoo, Finland, 2740
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Helsinki, Finland, 00029 HUS
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Jyvaskyla, Finland, 40100
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Kuopio, Finland, 70100
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Tampere, Finland, 33900
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Abbeville Cedex, France, 80142
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Albi Cedex 09, France, 81013
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Cholet, France, 49325
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Grenoble Cedex 09, France, 38043
Local Institution
Langres Cedex, France, 52206
Local Institution
Paris Cedex 18, France, 75018
Local Institution
Sisteron, France, 04203
Local Institution
Toulon Cedex 09, France, 83041
Local Institution
Berlin, Germany, 10117
Local Institution
Berlin, Germany, 12099
Local Institution
Berlin, Germany, 13353
Local Institution
Bonn, Germany, 53115
Local Institution
Essen, Germany, 45147
Local Institution
Frankfurt Am Main, Germany, 60590
Local Institution
Halle/Saale, Germany, 06097
Local Institution
Hamburg, Germany, 22527
Local Institution
Hamburg, Germany, 22299
Local Institution
Hamburg, Germany, 22291
Local Institution
Heidelberg, Germany, 69115
Local Institution
Heidelberg, Germany, 69120
Local Institution
Kassel, Germany, 34121
Local Institution
Koln, Germany, 51067
Local Institution
Leipzig, Germany, 04103
Local Institution
Magdeburg, Germany, 39112
Local Institution
Mainz, Germany, 55116
Local Institution
Mainz, Germany, 55131
Local Institution
Mannheim, Germany, 68167
Local Institution
Papenburg, Germany, 26871
Local Institution
Regensburg, Germany, 93053
Local Institution
Riesa, Germany, 01587
Local Institution
Witten, Germany, 58455
Local Institution
Wolmirstedt, Germany, 39326
Local Institution
Athens, Greece, 151 23
Local Institution
Larissa, Greece, 41 221
Local Institution
Thiva, Greece, 32200
Local Institution
Shatin, New Territories, Hong Kong
Local Institution
Chai Wan, Hong Kong
Local Institution
Hong Kong, Hong Kong, -----
Local Institution
Hyderabad, Andhra Pradesh, India, 500001
Local Institution
Bangalore, Karnataka, India, 560052
Local Institution
Banglore, Karnataka, India, 560054
Local Institution
Mysore, Karnataka, India, 570020
Local Institution
Mumbai, Maharashtra, India, 400052
Local Institution
Mumbai, Maharashtra, India, 400007
Local Institution
Nagpur, Maharashtra, India, 440012
Local Institution
Nashik, Maharashtra, India, 422002
Local Institution
Pune, Maharashtra, India, 411001
Local Institution
Dhantoli, Nagpur, India, 440012
Local Institution
Chennai, Tamil Nadu, India, 600081
Local Institution
Lucknow, Uttar Pradesh, India, 226003
Local Institution
Ahmedabad, India, 380060
Local Institution
Bangalore, India, 560034
Local Institution
Bikaner, India, 334 003
Local Institution
Indore, India, 452001
Local Institution
Jaipur, India, 302001
Local Institution
Kottayam, India, 686016
Local Institution
Pune, India, 411030
Local Institution
Jakarta, Dki Jakarta, Indonesia, 10430
Local Institution
Malang, Jawa-Timur, Indonesia, 65111
Local Institution
Bandung, Indonesia, 40161
Local Institution
Denpasar, Indonesia, 80114
Local Institution
Jakarta, Indonesia, 13310
Local Institution
Jakarta, Indonesia, 11420
Local Institution
Padang, Indonesia, 25137
Local Institution
Palembang, Indonesia, 30126
Local Institution
Surabaya, Indonesia, 60286
Local Institution
Yogyakarta, Indonesia, 55284
Local Institution
Afula, Israel, 18101
Local Institution
Ashkelon, Israel, 78278
Local Institution
Givatayim, Israel, 53583
Local Institution
Hadera, Israel, 38100
Local Institution
Haifa, Israel, 31096
Local Institution
Haifa, Israel, 34362
Local Institution
Holon, Israel, 58100
Local Institution
Nazareth, Israel, 16100
Local Institution
Nazareth, Israel, 16000
Local Institution
Petach-Tikva, Israel, 49100
Local Institution
Safed, Israel, 13100
Local Institution
Tel Aviv, Israel, 64239
Local Institution
Ascoli Piceno, Italy, 63100
Local Institution
Chieti, Italy, 66013
Local Institution
Genova, Italy, 16132
Local Institution
Isernia, Italy, 86170
Local Institution
Lido Di Camaiore, Italy, 55043
Local Institution
Palermo, Italy, 90127
Local Institution
Perugia, Italy, 06126
Local Institution
San Daniele De Friuli (Ud), Italy, 33038
Local Institution
Sassari, Italy, 07100
Local Institution
Goyang-Si, Gyeonggi-Do, Korea, Republic of, 411-773
Local Institution
Seongnam-Si, Gyeonggi-Do, Korea, Republic of, 463-707
Local Institution
Kuri-City, Kyunggi-Do, Korea, Republic of, 471-701
Local Institution
Busan, Korea, Republic of, 602-702
Local Institution
Daegu, Korea, Republic of, 700-721
Local Institution
Daejeon, Korea, Republic of, 302-718
Local Institution
Gwangju, Korea, Republic of, 501-757
Local Institution
Seoul, Korea, Republic of, 110-744
Local Institution
Seoul, Korea, Republic of, 143-729
Local Institution
Seoul, Korea, Republic of, 130-709
Local Institution
Johor Bahru, Johor, Malaysia, 80100
Local Institution
Cheras, Kuala Lumpur, Malaysia, 56000
Local Institution
Pulau Pinang, Pinang, Malaysia, 10990
Local Institution
Kuching, Sarawak, Malaysia, 93586
Local Institution
Kuala Lumpur, Malaysia, 50586
Local Institution
Kuala Lumpur, Malaysia, 59100
Local Institution
Mexico, Distrito Federal, Mexico, 14080
Local Institution
Mexico, Distrito Federal, Mexico, 06726
Local Institution
Atizapan De Zaragoza, Estado De Mexico, Mexico, 52975
Local Institution
Acapulco, Guerrero, Mexico, 39570
Local Institution
Guadalajara, Jalisco, Mexico, 44600
Local Institution
Guadalajara, Jalisco, Mexico, 44670
Local Institution
Zapopan, Jalisco, Mexico, 45200
Local Institution
Monterrey, Nuevo Leon, Mexico, 64240
Local Institution
San Luis Potosi, Slp, San Luis Potosi, Mexico, 78240
Local Institution
Culiacan, Sinaloa, Mexico, 80020
Local Institution
Hermosillo, Sonora, Mexico, 83190
Local Institution
Jalapa, Veracruz, Mexico, 91190
Local Institution
Aguascalientes, Mexico, 20230
Local Institution
Aguascalientes, Mexico, 20127
Local Institution
Chihuahua, Mexico, 31203
Local Institution
Durango, Mexico, 34080
Local Institution
Queretaro, Mexico, 76000
Local Institution
San Luis Potosi, Mexico, 78200
Local Institution
Fyllingsdal, Norway, 5145
Local Institution
Kongsberg, Norway, 3602
Local Institution
Oslo, Norway, 450
Local Institution
Oslo, Norway, 264
Local Institution
Naga City, Camarines Sur, Philippines, 4400
Local Institution
Binan, Laguna, Philippines, 4024
Local Institution
Iligan City, Lanao Del Norte, Philippines, 9200
Local Institution
Cagayan De Oro City, Philippines, 9000
Local Institution
Cavite, Philippines, 4114
Local Institution
Laoag City, Philippines, 2900
Local Institution
Manila, Philippines, 1000
Local Institution
Muntinlupa City, Philippines, 1780
Local Institution
Czestochowa, Poland, 42-200
Local Institution
Elblag, Poland, 82-300
Local Institution
Gdynia, Poland, 81-423
Local Institution
Gliwice, Poland, 44-100
Local Institution
Gniewkowo, Poland, 88-140
Local Institution
Grodzisk Mazowiecki, Poland, 05-825
Local Institution
Inowroclaw, Poland, 88-100
Local Institution
Kielce, Poland, 25-736
Local Institution
Krakow, Poland, 30-092
Local Institution
Krakow, Poland, 31-501
Local Institution
Lodz, Poland, 91-302
Local Institution
Piotrkow Trybunalski, Poland, 97-300
Local Institution
Plock, Poland, 09-402
Local Institution
Poznan, Poland, 60-539
Local Institution
Pulawy, Poland, 24-100
Local Institution
Siemianowice Slaskie, Poland, 41-100
Local Institution
Skierniewice, Poland, 96-100
Local Institution
Tarnow, Poland, 33-100
Local Institution
Warsaw, Poland, 00-217
Local Institution
Warszawa, Poland, 04-073
Local Institution
Warszawa, Poland, 03-242
Local Institution
Wegrow, Poland, 07-100
Local Institution
Zabrze, Poland, 41-800
Local Institution
Zarow, Poland, 58-130
Local Institution
Kaluga, Anenki, Russian Federation, 248007
Local Institution
Barnaul, Russian Federation, 656055
Local Institution
Chelyabinsk, Russian Federation, 454136
Local Institution
Ekaterinburg, Russian Federation, 620144
Local Institution
Ekaterinburg, Russian Federation, 620109
Local Institution
Kazan, Russian Federation, 420012
Local Institution
Kemerovo, Russian Federation, 650002
Local Institution
Krasnodar, Russian Federation, 350042
Local Institution
Moscow, Russian Federation, 109240
Local Institution
Moscow, Russian Federation, 121359
Local Institution
Moscow, Russian Federation, 129336
Local Institution
Moscow, Russian Federation, 119121
Local Institution
Moscow, Russian Federation, 121552
Local Institution
Moscow, Russian Federation, 125284
Local Institution
Moscow, Russian Federation, 125367
Local Institution
Moscow, Russian Federation, 111539
Local Institution
Moscow, Russian Federation, 127644
Local Institution
Moscow, Russian Federation, 117485
Local Institution
Moscow, Russian Federation, 105066
Local Institution
Moscow, Russian Federation, 129301
Local Institution
Moscow, Russian Federation, 101990
Local Institution
Moscow, Russian Federation, 143000
Local Institution
Nizhniy Novgorod, Russian Federation, 603035
Local Institution
Novosibirsk, Russian Federation, 630047
Local Institution
Perm, Russian Federation, 614107
Local Institution
Perm, Russian Federation, 614097
Local Institution
Ryazan, Russian Federation, 390026
Local Institution
Saint Petersburg, Russian Federation, 193079
Local Institution
Saint-Petersburg, Russian Federation, 190000
Local Institution
Saint-Petersburg, Russian Federation, 194291
Local Institution
Saint-Petersburg, Russian Federation, 191025
Local Institution
Saint-Petersburg, Russian Federation, 193144
Local Institution
Saint-Petersburg, Russian Federation, 194156
Local Institution
Samara, Russian Federation, 443070
Local Institution
Samara, Russian Federation, 443053
Local Institution
Saratov, Russian Federation, 410028
Local Institution
Saratov, Russian Federation, 410054
Local Institution
St.Petersburg, Russian Federation, 197198
Local Institution
St.Petersburg, Russian Federation, 195112
Local Institution
Tomsk, Russian Federation, 634012
Local Institution
Tumen, Russian Federation, 625023
Local Institution
Tver, Russian Federation, 170036
Local Institution
Yaroslavl, Russian Federation, 150062
Local Institution
Singapore, Singapore, 768828
Local Institution
Singapore, Singapore, 168752
Local Institution
Singapore, Singapore, 308433
Local Institution
Singapore, Singapore, 529889
Local Institution
Bloemfontein, Free State, South Africa, 9300
Local Institution
Bloemfontein, Free State, South Africa, 9301
Local Institution
Alberton, Gauteng, South Africa, 1450
Local Institution
Bellville, Cape Town, Western Cape, South Africa, 7530
Local Institution
Cape Town, Western Cape, South Africa, 7925
Local Institution
Somerset West, Western Cape, South Africa, 7130
Local Institution
Worcester, Western Cape, South Africa, 6850
Local Institution
Pretoria, South Africa, 41
Local Institution
Torrevieja, Alicante, Spain, 3186
Local Institution
Hospitalet De Llobregat, Barcelona, Spain, 8907
Local Institution
Lugo, Galicia, Spain, 27003
Local Institution
Albacete, Spain, 02006
Local Institution
Madrid, Spain, 28007
Local Institution
Madrid, Spain, 28034
Local Institution
Valencia, Spain, 46017
Local Institution
Goteborg, Sweden, 417 17
Local Institution
Goteborg, Sweden, 416 85
Local Institution
Molndal, Sweden, 431 80
Local Institution
Stockholm, Sweden, 111 57
Local Institution
Stockholm, Sweden, 141 86
Local Institution
Stockholm, Sweden, 118 83
Local Institution
Uppsala, Sweden, 751 85
Local Institution
Kaohsiung, Taiwan, 807
Local Institution
Taichung, Taiwan, 402
Local Institution
Tainan, Taiwan, 704
Local Institution
Taipei, Taiwan, 111
Local Institution
Taipei, Taiwan, 220
Local Institution
Taipei, Taiwan, 10507
Local Institution
Isparta, Turkey, 32100
Local Institution
Istanbul, Turkey, 34304
Local Institution
Istanbul, Turkey, 34390
Local Institution
Kirikkale, Turkey, 71100
Local Institution
Dnipropetrovsk, Ukraine, 49005
Local Institution
Donetsk, Ukraine, 83114
Local Institution
Kharkiv, Ukraine, 61029
Local Institution
Kharkiv, Ukraine, 61176
Local Institution
Kharkiv, Ukraine, 61002
Local Institution
Kharkiv, Ukraine, 61115
Local Institution
Kharkiv, Ukraine, 61018
Local Institution
Kyiv, Ukraine, 1023
Local Institution
Kyiv, Ukraine, 2660
Local Institution
Kyiv, Ukraine, 3680
Local Institution
Kyiv, Ukraine, 04114
Local Institution
Kyiv, Ukraine, 2091
Local Institution
Kyiv, Ukraine, 4107
Local Institution
Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
Local Institution
Chesterfield, Derbyshire, United Kingdom, S44 5BL
Local Institution
Basildon, Essex, United Kingdom, SS16 5NL
Local Institution
Romford, Essex, United Kingdom, RM7 0AG
Local Institution
Kirkcaldy, Fife, United Kingdom, KY2 5AH
Local Institution
London, Greater London, United Kingdom, SW17 ORE
Local Institution
Glasgow, Lanarkshire, United Kingdom, G11 6NT
Local Institution
Glasgow, Lanarkshire, United Kingdom, G51 4TF
Local Institution
Blackpool, Lancashire, United Kingdom, FY3 8NR
Local Institution
Northampton, Northamptonshire, United Kingdom, NN1 5BD
Local Institution
Worksop, Nottinghamshire, United Kingdom, S18 0BD
Local Institution
Craigavon, Portadown, United Kingdom, BT63 5QQ
Local Institution
Paisley, Renfrewshire, United Kingdom, PA2 9PN
Local Institution
Barnsley, South Yorkshire, United Kingdom, S75 2EP
Local Institution
Larbert, Stirlingshire, United Kingdom, FK5 4WR
Local Institution
Newcastle Upon, Tyne And Wear, United Kingdom, NE2 4HH
Local Institution
Birmingham, West Midlands, United Kingdom, B18 7QH
Local Institution
Chichester, West Sussex, United Kingdom, PO19 6SE