Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-mortality in Patients With Chronic Heart Failure (ATMOSPHERE)

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of Both Aliskiren Monotherapy and Aliskiren/Enalapril Combination Therapy Compared to Enalapril Monotherapy, on Morbidity and Mortality in Patients With Chronic Heart Failure (NYHA Class II - IV). The Study is Also Known as Aliskiren Trial of Minimizing OutcomeS in Patients With HEart Failure (ATMOSPHERE).

The study will evaluate the efficacy and safety of both aliskiren monotherapy and aliskiren/enalapril combination therapy as compared to enalapril monotherapy, on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Enalapril; Drug: Aliskiren

• Study Type: Interventional
• Enrollment (Actual): 7064
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1094AAD
    • Novartis Investigative Site
  • Cordoba, Argentina, X5022CPU
    • Novartis Investigative Site
  • Cordoba, Argentina, X5002AOQ
    • Novartis Investigative Site
  • Cordoba, Argentina, X5009BSN
    • Novartis Investigative Site
  • Cordoba, Argentina, X5004BAL
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000EVQ
    • Novartis Investigative Site
  • Cordoba, Argentina, X5003DCE
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000EPU
    • Novartis Investigative Site
  • Cordoba, Argentina, X5006IKK
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000FGG
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000AAI
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000AVI
    • Novartis Investigative Site
  • Cordoba, Argentina, X5220XAO
    • Novartis Investigative Site
  • Corrientes, Argentina, W3400
    • Novartis Investigative Site
  • Corrientes, Argentina, W3400CBI
    • Novartis Investigative Site
  • Salta, Argentina, 4400
    • Novartis Investigative Site
  • Buenos Aires
    • Bahia Blanca, Buenos Aires, Argentina, 8000
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1180AAX
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1408INH
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1416DRJ
      • Novartis Investigative Site
    • Coronel Suarez, Buenos Aires, Argentina, B7540GHD
      • Novartis Investigative Site
    • La Plata, Buenos Aires, Argentina, 1900
      • Novartis Investigative Site
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Novartis Investigative Site
    • Ramos Mejia, Buenos Aires, Argentina, B1704ETD
      • Novartis Investigative Site
    • San Isidro, Buenos Aires, Argentina, B1642DCD
      • Novartis Investigative Site
    • San Nicolas, Buenos Aires, Argentina, B2900DMH
      • Novartis Investigative Site
  • Cordoba
    • Córdoba, Cordoba, Argentina, X5152HQC
      • Novartis Investigative Site
    • Va Allende, Cordoba, Argentina, 5105
      • Novartis Investigative Site
    • Villa Maria, Cordoba, Argentina, X5220XAO
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  • Misiones
    • Posadas, Misiones, Argentina, N3300AHX
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  • San Miguel de Tucuman
    • Tucuman, San Miguel de Tucuman, Argentina, T4000ICL
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  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CXH
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    • Rosario, Santa Fe, Argentina, S2000DSV
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    • Rosario, Santa Fe, Argentina, S2001ODA
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    • Rosario, Santa Fe, Argentina, S2000DFD
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  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, T4000IFL
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• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
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  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
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    • Kingswood, New South Wales, Australia, 2747
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    • Wollongong, New South Wales, Australia, 2500
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  • Queensland
    • Auchenflower, Queensland, Australia, 4066
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    • Woolloongabba, Queensland, Australia, 4101
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    • Wooloongabba, Queensland, Australia, 4102
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  • South Australia
    • Bedford Park, South Australia, Australia, 5042
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  • Tasmania
    • Launceston, Tasmania, Australia, 7250
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  • Victoria
    • Geelong, Victoria, Australia, 3220
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    • Prahran, Victoria, Australia, 3181
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• Austria
  • Graz, Austria, A-8036
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  • Linz, Austria, A-4010
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  • Linz, Austria, 4010
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  • Salzburg, Austria, A-5020
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  • Vienna, Austria, 1140
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  • Vienna, Austria, 1030
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  • Wien, Austria, A-1090
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  • Wien, Austria, A-1160
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  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
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• Belgium
  • Anderlecht, Belgium, 1070
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  • Brugge, Belgium, 8000
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  • Brussels, Belgium, 1180
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  • Bruxelles, Belgium, 1200
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  • De Pinte, Belgium, 9840
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  • Eupen, Belgium, 4700
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  • Genk, Belgium, 3600
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  • Huy, Belgium, 4500
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  • Ieper, Belgium, 8900
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  • Leuven, Belgium, 3000
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  • Liege, Belgium, 4000
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  • Turnhout, Belgium, 2300
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• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60864-190
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    • Belo Horizonte, MG, Brazil, 30110-934
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  • PE
    • Recife, PE, Brazil, 50100-060
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  • PR
    • Campina Grande do Sul, PR, Brazil, 83430-000
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    • Curitiba, PR, Brazil, 80010-030
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    • Londrina, PR, Brazil, 86051-990
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  • RJ
    • Rio de Janeiro, RJ, Brazil, 22240-006
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    • Porto Alegre, RS, Brazil, 90020-090
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    • Porto Alegre, RS, Brazil, 90610-000
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    • Porto Alegre, RS, Brazil, 90560-030
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  • SP
    • Campinas, SP, Brazil, 13020-431
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    • Campinas, SP, Brazil, 13060-904
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    • Campinas, SP, Brazil, 13083-190
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    • Marilia, SP, Brazil, 17519-030
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    • São Paulo, SP, Brazil, 05403-900
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    • Tatuí, SP, Brazil, 18270-170
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• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
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  • New Brunswick
    • St. John, New Brunswick, Canada, E2L 4L2
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  • Ontario
    • Brampton, Ontario, Canada, L6Z 4N5
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    • Cambridge, Ontario, Canada, N1R 6V6
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    • Ottawa, Ontario, Canada, K1Y 4W7
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  • Quebec
    • Joliette, Quebec, Canada, J6E 6J2
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    • Montreal, Quebec, Canada, H1T 1C8
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    • Montreal, Quebec, Canada, H1T 3Y7
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    • Québec, Quebec, Canada, G1J 1Z6
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    • Sainte-Foy, Quebec, Canada, G1V 4G5
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• China
  • Baotou, China, 014040
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  • Beijing, China, 100044
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  • Beijing, China, 100029
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  • Beijing, China, 100020
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  • Beijing, China, 100034
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  • Beijing, China, 100050
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  • Beijing, China, 100028
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  • Guang zhou, China, 510080
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  • Jinan, China, 250012
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  • Shanghai, China, 200032
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  • Shanghai, China, 200025
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  • Shanghai, China, 200233
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  • Tianjin, China, 300142
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  • Xian, China, 710004
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  • Beijing
    • Beijing, Beijing, China, 100730
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    • Beijing, Beijing, China, 100088
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    • Beijing, Beijing, China, 100083
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  • Fujian
    • Fuzhou, Fujian, China, 350001
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  • Guangdong
    • Guangzhou, Guangdong, China, 510080
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    • Guangzhou, Guangdong, China, 510515
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  • Hebei
    • Shijiazhuang, Hebei, China, 050000
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  • Hubei
    • Wuhan, Hubei, China, 430022
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  • Jiangsu
    • Nanjing, Jiangsu, China
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    • Suzhou, Jiangsu, China, 215004
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  • Jilin
    • Changchun, Jilin, China, 130021
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  • Liaoning
    • Shenyang, Liaoning, China, 110003
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    • Shenyang, Liaoning, China, 110016
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  • Shanghai
    • Shanghai, Shanghai, China, 200011
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  • Tianjin
    • Tianjin, Tianjin, China, 300121
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  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
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    • Hangzhou, Zhejiang, China, 310009
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    • Hangzhou, Zhejiang, China, 310006
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    • Hangzhou, Zhejiang, China, 310013
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• Colombia
  • Barranquilla, Colombia
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  • Bogotá, Colombia
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  • Bogotá, Colombia, 00000
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  • Florida Blanca, Colombia
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  • Medellín, Colombia
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  • Antioquia
    • Medellín, Antioquia, Colombia
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  • Atlantico
    • Baranquilla, Atlantico, Colombia
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    • Barranquilla, Atlantico, Colombia
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  • Bolivar
    • Cartagena, Bolivar, Colombia
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  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 111411
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    • Bogotá, Cundinamarca, Colombia, 110111
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• Costa Rica
  • Alajuela, Costa Rica
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  • San Jose, Costa Rica, 1307-1000
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  • San Jose, Costa Rica, 272-1225
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  • San Jose, Costa Rica
    • Goicoechea, San Jose, Costa Rica, Costa Rica, 3184-1000
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• Czech Republic
  • Benesov, Czech Republic, 25601
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  • Brno, Czech Republic, 60200
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  • Cesky Krumlov, Czech Republic, 381 01
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  • Jindrichuv Hradec, Czech Republic, 377 01
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  • Kolín, Czech Republic, 280 02
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  • Kromeriz, Czech Republic, 767 01
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  • Louny, Czech Republic, 440 01
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  • Louny, Czech Republic
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  • Marianske lazne, Czech Republic, 353 01
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  • Ostrava, Czech Republic, 70200
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  • Plzen, Czech Republic, 323 00
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  • Praha 11, Czech Republic, 148 00
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  • Praha 2, Czech Republic, 128 08
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  • Praha 9, Czech Republic
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  • Pribram VIII, Czech Republic, 261 01
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  • Teplice, Czech Republic, 415 01
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  • Vyskov, Czech Republic, 68001
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• Denmark
  • Aalborg, Denmark, DK-9000
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  • Copenhagen, Denmark, 2100
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  • Copenhagen NV, Denmark, DK-2400
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  • Copenhagen S, Denmark, DK-2300
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  • Esbjerg, Denmark, DK-6700
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  • Fredericia, Denmark, 7000
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  • Frederiksberg, Denmark, DK-2000
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  • Glostrup, Denmark, DK-2600
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  • Hellerup, Denmark, DK-2900
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  • Helsingoer, Denmark, DK-3000
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  • Hillerød, Denmark, DK-3400
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  • Hjørring, Denmark, DK-9800
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  • Holbæk, Denmark, DK-4300
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  • Hvidovre, Denmark, DK-2650
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  • Køge, Denmark, DK-4600
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  • Næstved, Denmark, DK-4700
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  • Odense C, Denmark, DK-5000
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  • Randers NØ, Denmark, DK-8930
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  • Silkeborg, Denmark, 8600
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  • Svendborg, Denmark, DK-5700
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  • Viborg, Denmark, DK-8800
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  • Århus N, Denmark, DK-8200
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• Dominican Republic
  • San Cristobal, Dominican Republic
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  • Republica Dominicana
    • Santo Domingo, Republica Dominicana, Dominican Republic
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• Estonia
  • Parnu, Estonia, 80010
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  • Tallinn, Estonia, 13419
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  • Tallinn, Estonia, 10138
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  • Tartu, Estonia, 51014
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• Finland
  • Hyvinkää, Finland, FIN-05850
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  • Jyvaskyla, Finland, FIN-40620
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  • Seinajoki, Finland, 60200
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  • Tammisaari, Finland, 10600
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  • Turku, Finland, FIN-20520
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• France
  • Albi, France, 81013
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  • Angers, France, 49000
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  • Becon Les Granits, France, 49370
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  • Clichy, France, 92110
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  • Dijon, France, 21079
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  • Grenoble, France, 38043
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  • Marseille, France, 13915
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  • Marseille Cedex 05, France, 13385
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  • Paris, France, 75013
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  • Paris, France, 75571
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  • Pessac Cedex, France, 33604
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  • Saint-Etienne, France, 42055
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  • Vandoeuvre Les Nancy, France, 54511
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• Germany
  • Augsburg, Germany, 86150
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  • Bad Nauheim, Germany, 61231
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  • Bad Neustadt an der Saale, Germany, 97616
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  • Bensheim, Germany, 64625
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  • Berlin, Germany, 10367
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  • Berlin, Germany, 13353
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  • Berlin, Germany, 10789
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  • Berlin, Germany, 12552
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  • Bochum, Germany, 44791
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  • Bonn, Germany, 53127
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  • Bonn, Germany, 53115
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  • Bonn, Germany, 53225
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  • Celle, Germany, 29223
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  • Chemnitz, Germany, 09113
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  • Chemnitz, Germany, 09126
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  • Chemnitz, Germany, 09116
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  • Coburg, Germany, 96450
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  • Darmstadt, Germany, 64283
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  • Dessau-Roßlau, Germany, 06846
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  • Dinkelsbühl, Germany, 91550
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  • Dorsten, Germany, 46282
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  • Dresden, Germany, 01309
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  • Markkleeberg, Germany, 04416
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  • Solingen, Germany, 42651
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  • Stade, Germany, 21682
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  • Stuttgart, Germany, 70378
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  • Stuttgart, Germany, 70372
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  • Wedel, Germany, 22880
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  • Witten, Germany, 58455
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  • Wuerzburg, Germany, 97078
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  • Zwickau, Germany, 08056
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  • Lower Saxony
    • Winsen (Luhe), Lower Saxony, Germany, 21423
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• Greece
  • Athens, Greece, GR 11527
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  • Athens, Greece, 115 28
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  • Athens, Greece, 124 62
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  • Chios, Greece, 82100
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  • Edessa, Greece, 58200
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  • GR
    • Athens, GR, Greece, 115 27
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    • Thessaloniki, GR, Greece, 570 10
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    • Thessaloniki, GR, Greece, 546 36
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• India
  • Bangalore, India, 560 034
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  • Hyderabad, India, 500 063
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  • Hyderabad, India, 500044
    • Novartis Investigative Site
  • Lucknow, India, 226003
    • Novartis Investigative Site
  • Mumbai, India, 400 050
    • Novartis Investigative Site
  • New Delhi, India, 110044
    • Novartis Investigative Site
  • Noida, India, 201301
    • Novartis Investigative Site
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Novartis Investigative Site
    • Hyderabad, Andhra Pradesh, India, 500012
      • Novartis Investigative Site
    • Secunderabad, Andhra Pradesh, India, 500003
      • Novartis Investigative Site
    • Vijayawada, Andhra Pradesh, India, 520 008
      • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Novartis Investigative Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 051
      • Novartis Investigative Site
  • Karnataka
    • Bangalore, Karnataka, India, 560099
      • Novartis Investigative Site
    • Bangalore, Karnataka, India, 560 052
      • Novartis Investigative Site
    • Manipal, Karnataka, India, 576104
      • Novartis Investigative Site
  • Kerela
    • Trivandrum, Kerela, India, 695002
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 022
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 400 012
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 440010
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 440012
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 400012
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 400 008
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 440 010
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411004
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411 019
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411 011
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411011
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411 044
      • Novartis Investigative Site
  • New Delhi
    • Delhi, New Delhi, India, 110065
      • Novartis Investigative Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302001
      • Novartis Investigative Site
    • Jaipur, Rajasthan, India, 302024
      • Novartis Investigative Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600100
      • Novartis Investigative Site
    • Coimbatore, Tamil Nadu, India, 641014
      • Novartis Investigative Site
    • Madurai, Tamil Nadu, India, 625107
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Novartis Investigative Site
    • Lucknow, Uttar Pradesh, India, 226005
      • Novartis Investigative Site
• Ireland
  • Co Dublin, Ireland
    • Novartis Investigative Site
  • Dublin, Ireland, 9
    • Novartis Investigative Site
  • Dublin, Ireland
    • Novartis Investigative Site
  • Dublin 7, Ireland
    • Novartis Investigative Site
  • Galway, Ireland
    • Novartis Investigative Site
• Italy
  • (pv)
    • Montescano, (pv), Italy, 27040
      • Novartis Investigative Site
    • Pavia, (pv), Italy, 27100
      • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • AR
    • Arezzo, AR, Italy, 52100
      • Novartis Investigative Site
    • Cortona, AR, Italy, 52044
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24128
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
    • Lumezzane, BS, Italy, 25065
      • Novartis Investigative Site
  • CH
    • Chieti, CH, Italy, 66100
      • Novartis Investigative Site
  • CS
    • Cosenza, CS, Italy, 87100
      • Novartis Investigative Site
  • FC
    • Forlì, FC, Italy, 47100
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • FG
    • Foggia, FG, Italy, 71100
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50143
      • Novartis Investigative Site
  • IS
    • Pozzilli, IS, Italy, 86077
      • Novartis Investigative Site
  • LE
    • Casarano, LE, Italy, 73042
      • Novartis Investigative Site
  • LI
    • Cecina, LI, Italy, 57023
      • Novartis Investigative Site
  • LU
    • Castelnuovo di Garfagnana, LU, Italy, 55032
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20138
      • Novartis Investigative Site
    • Passirana di Rho, MI, Italy, 20017
      • Novartis Investigative Site
  • MN
    • Pieve di Coriano, MN, Italy
      • Novartis Investigative Site
  • MS
    • Massa, MS, Italy, 54100
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RA
    • Cotignola, RA, Italy, 48010
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00184
      • Novartis Investigative Site
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
    • Roma, RM, Italy, 00169
      • Novartis Investigative Site
  • RN
    • Rimini, RN, Italy, 47900
      • Novartis Investigative Site
  • SA
    • Cava De' Tirreni, SA, Italy, 84013
      • Novartis Investigative Site
  • SI
    • Poggibonsi, SI, Italy, 53036
      • Novartis Investigative Site
  • SO
    • Sondalo, SO, Italy, 23035
      • Novartis Investigative Site
  • SP
    • Sarzana, SP, Italy, 19038
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • TR
    • Terni, TR, Italy, 05100
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34149
      • Novartis Investigative Site
    • Trieste, TS, Italy, 34142
      • Novartis Investigative Site
  • TV
    • Vittorio Veneto, TV, Italy, 31029
      • Novartis Investigative Site
  • UD
    • San Daniele Del Friuli, UD, Italy, 33038
      • Novartis Investigative Site
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
  • VA
    • Tradate, VA, Italy, 21049
      • Novartis Investigative Site
  • VR
    • San Bonifacio, VR, Italy, 37047
      • Novartis Investigative Site
• Japan
  • Fukushima, Japan, 960-8251
    • Novartis Investigative Site
  • Nagasaki, Japan, 850-8555
    • Novartis Investigative Site
  • Saga, Japan, 849-8501
    • Novartis Investigative Site
  • Toyama, Japan, 930-0194
    • Novartis Investigative Site
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8560
      • Novartis Investigative Site
    • Seto-city, Aichi, Japan, 489-8642
      • Novartis Investigative Site
  • Chiba
    • Chiba-city, Chiba, Japan, 260-8677
      • Novartis Investigative Site
    • Inba-gun, Chiba, Japan, 270-1694
      • Novartis Investigative Site
  • Fukuoka
    • Chikushino-city, Fukuoka, Japan, 818-8502
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 814-0180
      • Novartis Investigative Site
    • Iizuka-city, Fukuoka, Japan, 820-8505
      • Novartis Investigative Site
    • Kurume-city, Fukuoka, Japan, 830-8577
      • Novartis Investigative Site
  • Gifu
    • Ogaki-city, Gifu, Japan, 503-8502
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima-city, Hiroshima, Japan, 734-8551
      • Novartis Investigative Site
    • Kure, Hiroshima, Japan, 737-0023
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 063-0005
      • Novartis Investigative Site
  • Hyogo
    • Amagasaki-city, Hyogo, Japan, 660-8550
      • Novartis Investigative Site
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 311-3193
      • Novartis Investigative Site
    • Hitachinaka, Ibaraki, Japan, 312-0057
      • Novartis Investigative Site
    • Tsukuba-city, Ibaraki, Japan, 305-8576
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8650
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 210-0852
      • Novartis Investigative Site
    • Sagamihara-city, Kanagawa, Japan, 252-0375
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 232-0024
      • Novartis Investigative Site
    • Yokosuka, Kanagawa, Japan, 238-8567
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Novartis Investigative Site
  • Nara
    • Kashihara-city, Nara, Japan, 634-8522
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 702-8055
      • Novartis Investigative Site
  • Osaka
    • Izumisano-city, Osaka, Japan, 598-8577
      • Novartis Investigative Site
    • Kita-ku, Osaka, Japan, 530-0001
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 545-8586
      • Novartis Investigative Site
  • Saga
    • Ureshino, Saga, Japan, 843-0393
      • Novartis Investigative Site
  • Shimane
    • Hamada, Shimane, Japan, 697-8511
      • Novartis Investigative Site
  • Tokushima
    • Komatsushima-city, Tokushima, Japan, 773-8502
      • Novartis Investigative Site
    • Tokushima-city, Tokushima, Japan, 770-8503
      • Novartis Investigative Site
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0006
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Novartis Investigative Site
  • Yamaguchi
    • Hofu, Yamaguchi, Japan, 747-8511
      • Novartis Investigative Site
    • Shunan-city, Yamaguchi, Japan, 745-8522
      • Novartis Investigative Site
    • Ube, Yamaguchi, Japan, 755-8505
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Novartis Investigative Site
  • Daejeon, Korea, Republic of, 302-241
    • Novartis Investigative Site
  • Gwangju, Korea, Republic of, 501-757
    • Novartis Investigative Site
  • Incheon, Korea, Republic of, 405-760
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 143-729
    • Novartis Investigative Site
  • Taegu, Korea, Republic of, 700 - 721
    • Novartis Investigative Site
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 152-703
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03722
      • Novartis Investigative Site
• Latvia
  • Daugavpils, Latvia, LV-5401
    • Novartis Investigative Site
  • Riga, Latvia, LV-1038
    • Novartis Investigative Site
  • Riga, Latvia, 1012
    • Novartis Investigative Site
  • Riga, Latvia, LV-1012
    • Novartis Investigative Site
• Lithuania
  • Kaunas, Lithuania, LT-47144
    • Novartis Investigative Site
  • Klaipeda, Lithuania, LT-92288
    • Novartis Investigative Site
  • Vilnius, Lithuania, 08661
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, 50009
      • Novartis Investigative Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Novartis Investigative Site
  • Querétaro, Mexico, 76000
    • Novartis Investigative Site
  • San Luis Potosi, Mexico, 78200
    • Novartis Investigative Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Novartis Investigative Site
    • Zapopan, Jalisco, Mexico, 45200
      • Novartis Investigative Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64710
      • Novartis Investigative Site
    • Monterrey, Nuevo León, Mexico, 64060
      • Novartis Investigative Site
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, CP:83230
      • Novartis Investigative Site
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Novartis Investigative Site
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Amsterdam, Netherlands, 1061 AE
    • Novartis Investigative Site
  • Amsterdam, Netherlands, 1023 NL
    • Novartis Investigative Site
  • Amsterdam, Netherlands, 1091 HA
    • Novartis Investigative Site
  • Apeldoorn, Netherlands, 7334 DZ
    • Novartis Investigative Site
  • Deventer, Netherlands, 7416 SE
    • Novartis Investigative Site
  • Dirksland, Netherlands, 3247 BW
    • Novartis Investigative Site
  • Enschede, Netherlands, 7513 ER
    • Novartis Investigative Site
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • Haarlem, Netherlands, 2035 RC
    • Novartis Investigative Site
  • Heerlen, Netherlands, 6419 PC
    • Novartis Investigative Site
  • Leeuwarden, Netherlands, 8934 AD
    • Novartis Investigative Site
  • Leiderdorp, Netherlands, NL-2353 GA
    • Novartis Investigative Site
  • Meppel, Netherlands, 7943 KA
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3083 AN
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3045 PM
    • Novartis Investigative Site
  • Venlo, Netherlands, 5912 BL
    • Novartis Investigative Site
  • Wildervank, Netherlands, 9648 BE
    • Novartis Investigative Site
  • Zutphen, Netherlands, 7207 AE
    • Novartis Investigative Site
  • Zwolle, Netherlands, 8011 JW
    • Novartis Investigative Site
• Norway
  • Oslo, Norway, 0514
    • Novartis Investigative Site
  • Trondheim, Norway, 7006
    • Novartis Investigative Site
  • Tønsberg, Norway, 3116
    • Novartis Investigative Site
• Peru
  • Lima, Peru, LIMA 39
    • Novartis Investigative Site
  • La Libertad
    • Trujillo, La Libertad, Peru
      • Novartis Investigative Site
  • Lambayeque
    • Chiclayo, Lambayeque, Peru
      • Novartis Investigative Site
  • Lima
    • Bellavista, Lima, Peru, CALLAO 02
      • Novartis Investigative Site
    • Cercado de Lima, Lima, Peru, 01
      • Novartis Investigative Site
    • Jesus Maria, Lima, Peru, 11
      • Novartis Investigative Site
    • Miraflores, Lima, Peru, 18
      • Novartis Investigative Site
    • San Borja, Lima, Peru, 41
      • Novartis Investigative Site
    • San Isidro, Lima, Peru, 27
      • Novartis Investigative Site
    • San Juan de Miraflores, Lima, Peru, 29
      • Novartis Investigative Site
• Poland
  • Bytom, Poland, 41-902
    • Novartis Investigative Site
  • Chorzow, Poland, 41-506
    • Novartis Investigative Site
  • Gdansk, Poland, 80-180
    • Novartis Investigative Site
  • Gdynia, Poland, 81-423
    • Novartis Investigative Site
  • Gdynia, Poland, 81-519
    • Novartis Investigative Site
  • Gliwice, Poland, 44-100
    • Novartis Investigative Site
  • Grodzisk Mazowiecki, Poland, 05-825
    • Novartis Investigative Site
  • Katowice, Poland, 40-084
    • Novartis Investigative Site
  • Katowice, Poland, 40-040
    • Novartis Investigative Site
  • Klodzko, Poland, 57-300
    • Novartis Investigative Site
  • Krakow, Poland, 30-053
    • Novartis Investigative Site
  • Kraków, Poland, 31-501
    • Novartis Investigative Site
  • Lomza, Poland, 18-104
    • Novartis Investigative Site
  • Olawa, Poland, 55-200
    • Novartis Investigative Site
  • Opole, Poland, 45-706
    • Novartis Investigative Site
  • Ostrow Wielkopolski, Poland, 63-400
    • Novartis Investigative Site
  • Ostrowiec Swietokrzyski, Poland, 27-400
    • Novartis Investigative Site
  • Piotrkow Trybunalski, Poland, 97-300
    • Novartis Investigative Site
  • Plock, Poland, 09-402
    • Novartis Investigative Site
  • Poznan, Poland, 61-485
    • Novartis Investigative Site
  • Sandomierz, Poland, 27-600
    • Novartis Investigative Site
  • Tarnow, Poland, 33-100
    • Novartis Investigative Site
  • Torun, Poland, 87-100
    • Novartis Investigative Site
  • Warszawa, Poland, 04-628
    • Novartis Investigative Site
  • Warszawa, Poland, 03-242
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-349
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-981
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-420
    • Novartis Investigative Site
  • Wroclaw, Poland, 52-612
    • Novartis Investigative Site
  • Zabrze, Poland, 41-800
    • Novartis Investigative Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Novartis Investigative Site
  • Aveiro, Portugal, 3814-501
    • Novartis Investigative Site
  • Carnaxide, Portugal, 2799-523
    • Novartis Investigative Site
  • Coimbra, Portugal, 3000-075
    • Novartis Investigative Site
  • Faro, Portugal, 8000-386
    • Novartis Investigative Site
  • Lisboa, Portugal, 1600-190
    • Novartis Investigative Site
  • Lisboa, Portugal, 1769-001
    • Novartis Investigative Site
  • Lisboa, Portugal, 1495-005
    • Novartis Investigative Site
  • Penafiel, Portugal, 4564-007
    • Novartis Investigative Site
  • Porto, Portugal, 4200-319
    • Novartis Investigative Site
• Puerto Rico
  • Humacao, Puerto Rico, 00791
    • Novartis Investigative Site
  • Ponce, Puerto Rico, 00717
    • Novartis Investigative Site
  • San Juan, Puerto Rico, 00936-6528
    • Novartis Investigative Site
• Romania
  • Baia Mare, Romania, 430123
    • Novartis Investigative Site
  • Brasov, Romania, 500281
    • Novartis Investigative Site
  • Brasov, Romania, 500427
    • Novartis Investigative Site
  • Cluj Napoca, Romania, 400006
    • Novartis Investigative Site
  • Cluj-Napoca, Romania, 400347
    • Novartis Investigative Site
  • Iasi, Romania, 700547
    • Novartis Investigative Site
  • Oradea, Romania, 410169
    • Novartis Investigative Site
  • Pitesti, Romania, 110114
    • Novartis Investigative Site
  • Targu Mures, Romania, 540096
    • Novartis Investigative Site
  • Timisoara, Romania, 300736
    • Novartis Investigative Site
  • Timisoara, Romania, 300310
    • Novartis Investigative Site
  • District 1
    • Bucharest, District 1, Romania, 012064
      • Novartis Investigative Site
    • Bucharest, District 1, Romania, 012051
      • Novartis Investigative Site
  • District 2
    • Bucharest, District 2, Romania, 021705
      • Novartis Investigative Site
  • Jud Iasi
    • Iasi, Jud Iasi, Romania, 700005
      • Novartis Investigative Site
  • Jud. Iasi
    • Iasi, Jud. Iasi, Romania, 700506
      • Novartis Investigative Site
  • Mures
    • Targu Mures, Mures, Romania, 540136
      • Novartis Investigative Site
  • jud Mures
    • Targu Mures, jud Mures, Romania, 540043
      • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656055
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454021
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454047
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454048
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454000
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation, 620137
    • Novartis Investigative Site
  • Izhevsk, Russian Federation, 426009
    • Novartis Investigative Site
  • Kirov, Russian Federation, 610014
    • Novartis Investigative Site
  • Krasnodar, Russian Federation, 350063
    • Novartis Investigative Site
  • Kursk, Russian Federation, 305035
    • Novartis Investigative Site
  • Lubertsi, Russian Federation, 140006
    • Novartis Investigative Site
  • Moscow, Russian Federation, 121359
    • Novartis Investigative Site
  • Moscow, Russian Federation
    • Novartis Investigative Site
  • Moscow, Russian Federation, 105229
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119992
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127473
    • Novartis Investigative Site
  • Moscow, Russian Federation, 117292
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129301
    • Novartis Investigative Site
  • Moscow, Russian Federation, 111539
    • Novartis Investigative Site
  • Moscow, Russian Federation, 111020
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115432
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603018
    • Novartis Investigative Site
  • Novosibirsk, Russian Federation, 630047
    • Novartis Investigative Site
  • Novosibirsk, Russian Federation, 630075
    • Novartis Investigative Site
  • Novosibirsk, Russian Federation, 630089
    • Novartis Investigative Site
  • Omsk, Russian Federation, 644018
    • Novartis Investigative Site
  • Perm, Russian Federation, 614097
    • Novartis Investigative Site
  • Pushkin,St-Petersburg, Russian Federation, 196601
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390026
    • Novartis Investigative Site
  • S.-Petersburg, Russian Federation, 196247
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410028
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 191119
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 198013
    • Novartis Investigative Site
  • Tyumen, Russian Federation, 625026
    • Novartis Investigative Site
  • Volgograd, Russian Federation, 400008
    • Novartis Investigative Site
  • Volgograd, Russian Federation, 400001
    • Novartis Investigative Site
  • Voronezh, Russian Federation, 394065
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150030
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150062
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150000
    • Novartis Investigative Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Novartis Investigative Site
  • Bratislava, Slovakia, 81369
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 01
    • Novartis Investigative Site
  • Kosice, Slovakia, 04001
    • Novartis Investigative Site
  • Lucenec, Slovakia, 98439
    • Novartis Investigative Site
  • Piestany, Slovakia, 921 01
    • Novartis Investigative Site
  • Presov, Slovakia, 080 01
    • Novartis Investigative Site
  • Trebisov, Slovakia, 075 01
    • Novartis Investigative Site
  • Trencin, Slovakia, 911 01
    • Novartis Investigative Site
  • Zilina, Slovakia, 012 07
    • Novartis Investigative Site
  • Slovak Republic
    • Bratislava, Slovak Republic, Slovakia, 826 06
      • Novartis Investigative Site
    • Bratislava, Slovak Republic, Slovakia, 812 72
      • Novartis Investigative Site
    • Komarno, Slovak Republic, Slovakia, 94575
      • Novartis Investigative Site
    • Kosice, Slovak Republic, Slovakia, 040 01
      • Novartis Investigative Site
    • Levice, Slovak Republic, Slovakia, 93401
      • Novartis Investigative Site
    • Nitra, Slovak Republic, Slovakia, 949 01
      • Novartis Investigative Site
    • Zilina, Slovak Republic, Slovakia, 010 01
      • Novartis Investigative Site
    • Zilina, Slovak Republic, Slovakia, 08001
      • Novartis Investigative Site
  • Slovak republic
    • Kosice, Slovak republic, Slovakia, 04166
      • Novartis Investigative Site
    • Povazska Bystrica, Slovak republic, Slovakia, 01701
      • Novartis Investigative Site
    • Presov, Slovak republic, Slovakia, 08101
      • Novartis Investigative Site
    • Stropkov, Slovak republic, Slovakia, 09101
      • Novartis Investigative Site
• South Africa
  • Benoni, South Africa
    • Novartis Investigative Site
  • Boksburg, South Africa
    • Novartis Investigative Site
  • Centurion, South Africa, 4001
    • Novartis Investigative Site
  • Johannesburg, South Africa, 2157
    • Novartis Investigative Site
  • Western Cape, South Africa, 7130
    • Novartis Investigative Site
  • Worcester, South Africa, 6850
    • Novartis Investigative Site
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28049
    • Novartis Investigative Site
  • Andalucia
    • Sanlucar de Barrameda, Andalucia, Spain, 11540
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
    • Utrera, Andalucia, Spain, 41710
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Novartis Investigative Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Cadiz
    • Villamartin, Cadiz, Spain, 11650
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Tarragona, Catalunya, Spain, 43005
      • Novartis Investigative Site
  • Cataluña
    • Tortosa, Cataluña, Spain, 43500
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03004
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Novartis Investigative Site
    • Valdemoro, Madrid, Spain, 28342
      • Novartis Investigative Site
• Sweden
  • Falun, Sweden, 791 82
    • Novartis Investigative Site
  • Göteborg, Sweden, 416 85
    • Novartis Investigative Site
  • Karlstad, Sweden, 681 85
    • Novartis Investigative Site
  • Linkoping, Sweden, 581 85
    • Novartis Investigative Site
  • Lund, Sweden, SE-222 21
    • Novartis Investigative Site
  • Malmo, Sweden, SE 211 36
    • Novartis Investigative Site
  • Malmö, Sweden, 205 02
    • Novartis Investigative Site
  • Malmö, Sweden, 214 22
    • Novartis Investigative Site
  • Mölndal, Sweden, 431 80
    • Novartis Investigative Site
  • Nässjö, Sweden, SE 571 31
    • Novartis Investigative Site
  • Skelleftea, Sweden, 931 86
    • Novartis Investigative Site
  • Stockholm, Sweden, 111 57
    • Novartis Investigative Site
  • Stockholm, Sweden, 17176
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-111 35
    • Novartis Investigative Site
  • Stockholm, Sweden, 112 81
    • Novartis Investigative Site
  • Sundsvall, Sweden, 851 86
    • Novartis Investigative Site
  • Sundsvall, Sweden, 852 31
    • Novartis Investigative Site
  • Umeå, Sweden, 901 85
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
  • Västerås, Sweden, s-721 89
    • Novartis Investigative Site
  • Örebro, Sweden, 701 85
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Bellinzona, Switzerland, 6500
    • Novartis Investigative Site
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Biel, Switzerland, 2500
    • Novartis Investigative Site
  • Bruderholz, Switzerland, 4101
    • Novartis Investigative Site
  • Lugano, Switzerland, 6903
    • Novartis Investigative Site
  • Olten, Switzerland, 4600
    • Novartis Investigative Site
  • Winterthur, Switzerland, 8401
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Lin-Kou, Taiwan, 33305
    • Novartis Investigative Site
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 104
    • Novartis Investigative Site
  • Tainan
    • Yongkang, Tainan, Taiwan, 71004
      • Novartis Investigative Site
  • Taiwan ROC
    • Tainan 704, Taiwan ROC, Taiwan, 70403
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Aydin, Turkey, 09100
    • Novartis Investigative Site
  • Balcova / Izmir, Turkey, 35340
    • Novartis Investigative Site
  • Etlik / Ankara, Turkey, 06018
    • Novartis Investigative Site
  • Fatih / Istanbul, Turkey, 34098
    • Novartis Investigative Site
  • Istanbul, Turkey, 34304
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Kinikli / Denizli, Turkey, 20070
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Novartis Investigative Site
  • Sivas, Turkey, 58140
    • Novartis Investigative Site
• United Kingdom
  • Cardiff, United Kingdom, CF5 4AD
    • Novartis Investigative Site
  • Chesterfield, United Kingdom, S44 5BL
    • Novartis Investigative Site
  • Colchester, United Kingdom, CO4 5JL
    • Novartis Investigative Site
  • East Yorkshire, United Kingdom, HU16 5JQ
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G51 4TF
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L14 3PE
    • Novartis Investigative Site
  • London, United Kingdom, SE1 7EH
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0RE
    • Novartis Investigative Site
  • Manchester, United Kingdom, M23 9LT
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • Swindon, United Kingdom, SN3 6BB
    • Novartis Investigative Site
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Novartis Investigative Site
  • Llanelli
    • Dafen, Llanelli, United Kingdom, SA14 8QF
      • Novartis Investigative Site
  • Surrey
    • Addlestone, Surrey, United Kingdom, KT15 2BH
      • Novartis Investigative Site
  • West Sussex
    • Chichester, West Sussex, United Kingdom, PO19 6SE
      • Novartis Investigative Site
    • Worthing, West Sussex, United Kingdom, BN11 2DH
      • Novartis Investigative Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Novartis Investigative Site
    • Mobile, Alabama, United States, 36608
      • Novartis Investigative Site
    • Mobile, Alabama, United States, 36693
      • Novartis Investigative Site
  • Arizona
    • Tucson, Arizona, United States, 85723-0001
      • Novartis Investigative Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Novartis Investigative Site
    • Little Rock, Arkansas, United States, 72204
      • Novartis Investigative Site
    • Little Rock, Arkansas, United States, 72205
      • Novartis Investigative Site
    • Pine Bluff, Arkansas, United States, 71603
      • Novartis Investigative Site
    • Searcy, Arkansas, United States, 72143
      • Novartis Investigative Site
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
    • French Camp, California, United States, 95231
      • Novartis Investigative Site
    • Inglewood, California, United States, 90301
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90073
      • Novartis Investigative Site
    • Modesto, California, United States, 95355
      • Novartis Investigative Site
    • Northridge, California, United States, 91325
      • Novartis Investigative Site
    • Sacramento, California, United States, 95825
      • Novartis Investigative Site
    • San Diego, California, United States, 92123
      • Novartis Investigative Site
    • Santa Monica, California, United States, 90404
      • Novartis Investigative Site
    • Westlake Village, California, United States, 91361
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Novartis Investigative Site
    • Littleton, Colorado, United States, 80120
      • Novartis Investigative Site
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Novartis Investigative Site
    • Daytona Beach, Florida, United States, 32117
      • Novartis Investigative Site
    • Fort Lauderdale, Florida, United States, 33316
      • Novartis Investigative Site
    • Hollywood, Florida, United States, 33021
      • Novartis Investigative Site
    • Jacksonville Beach, Florida, United States, 32050
      • Novartis Investigative Site
    • Miami Lakes, Florida, United States, 33014
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32803
      • Novartis Investigative Site
    • Wellington, Florida, United States, 33449
      • Novartis Investigative Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Novartis Investigative Site
    • Augusta, Georgia, United States, 30904
      • Novartis Investigative Site
  • Illinois
    • Gillespie, Illinois, United States, 62033
      • Novartis Investigative Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70121
      • Novartis Investigative Site
    • Slidell, Louisiana, United States, 70458
      • Novartis Investigative Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Novartis Investigative Site
  • Michigan
    • Southfield, Michigan, United States, 48075
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68198
      • Novartis Investigative Site
  • New Jersey
    • Elmer, New Jersey, United States, 08318
      • Novartis Investigative Site
  • New York
    • Laurelton, New York, United States, 11422
      • Novartis Investigative Site
    • Stony Brook, New York, United States, 11794
      • Novartis Investigative Site
    • Wiliamsville, New York, United States, 14221
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Novartis Investigative Site
  • Ohio
    • Marion, Ohio, United States, 43302
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Novartis Investigative Site
    • Varnville, South Carolina, United States, 29944
      • Novartis Investigative Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Novartis Investigative Site
    • Memphis, Tennessee, United States, 38120
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37212
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37205
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75226
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • Houston, Texas, United States, 77021
      • Novartis Investigative Site
  • Washington
    • Everett, Washington, United States, 98208
      • Novartis Investigative Site
    • Kirkland, Washington, United States, 98034
      • Novartis Investigative Site
• Venezuela
  • Distrito Capital
    • Caracas, Distrito Capital, Venezuela, 1010
      • Novartis Investigative Site
    • Caracas, Distrito Capital, Venezuela, 1040
      • Novartis Investigative Site
    • Caracas, Distrito Capital, Venezuela, 1060
      • Novartis Investigative Site
  • Edo. Carabobo
    • Valencia, Edo. Carabobo, Venezuela, 2001
      • Novartis Investigative Site
  • Estado Anzoátegui
    • Barcelona, Estado Anzoátegui, Venezuela, 6001
      • Novartis Investigative Site
  • Estado Bolívar
    • Puerto Ordaz, Estado Bolívar, Venezuela, 8050
      • Novartis Investigative Site
  • Estado Miranda
    • Caracas, Estado Miranda, Venezuela, 1061
      • Novartis Investigative Site
  • Estado Sucre
    • Cumana, Estado Sucre, Venezuela, 6101
      • Novartis Investigative Site
  • Estado Zulia
    • Maracaibo, Estado Zulia, Venezuela, 4011
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

1. Patients ≥ 18 years of age, male or female.

2. Patients with a diagnosis of chronic heart failure (NYHA

   Class II - IV):

   1. LVEF ≤ 35% at Visit 1 (local measurement, within the past 6 months assessed by echocardiography, multiple uptake gated acquisition scan (MUGA), computerized tomography(CT) scan, magnetic resonance imaging (MRI) or ventricular angiography)
   2. Elevated BNP or NT-proBNP at Visit 1:

   BNP ≥ 150 pg/mL (or BNP ≥ 100 pg/mL and unplanned hospitalization for HF within the last 12 months prior to Visit 1) (according to local measurement). OR NT-proBNP ≥ 600 pg/mL (or NT-proBNP ≥ 400 pg/mL and unplanned hospitalization for HF within the last 12 months prior to Visit 1) (according to local measurement).

3. Patients had to be treated with an ACEI at a stable dose enalapril 10 mg daily at least or any other ACEI, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; based on equivalent doses, for at least 4 weeks prior to Visit 1
4. Patients had to be treated with a beta-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose, according to local guidelines, or in absence of that medication, the reason should be documented).
5. Written informed consent to participate in the study and ability to comply with all requirements.

Exclusion Criteria

Patients with any of the following were to be excluded from participation in the study:

1. History of hypersensitivity to any of the study drugs including history or allergy to ACEIs as well as known or suspected contraindications to the study drugs or previous history of intolerance to high doses of ACEIs during up- titration process.
2. Patients treated concomitantly with both an ARB and an aldosterone antagonist in addition to study drug at Visit 1.
3. Current acute decompensated HF (defined as an acute exacerbation of a chronic heart failure status manifested by typical signs and symptoms of HF like dyspnea, fatigue etc., that may require IV therapy with diuretics, vasodilators and/or inotropic drugs).
4. Symptomatic hypotension and/or less than 95 mmHg systolic blood pressure (SBP) at Visit 1 and/or less than 90 mmHg SBP at Visit 4.
5. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months prior to Visit 1.
6. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
7. Right heart failure due to severe pulmonary disease.
8. Patients with Diabetes Mellitus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Aliskiren / Enalapril; Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg film-coated tablets and administered orally.	Drug: Enalapril; Enalapril 10 mg film-coated tablet and administered orally.; Drug: Aliskiren; Aliskiren 150 mg titrated to 300 mg film-coated tablet and administered orally.; Other Names: SPP100
Experimental: Aliskiren; Aliskiren monotherapy - 150 mg titrated to 300 mg film-coated tablets and administered orally.	Drug: Aliskiren; Aliskiren 150 mg titrated to 300 mg film-coated tablet and administered orally.; Other Names: SPP100
Active Comparator: Enalapril; Enalapril monotherapy -10 mg film-coated tablet and administered orally.	Drug: Enalapril; Enalapril 10 mg film-coated tablet and administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Had First Occurrence of the Composite Endpoint, Which is Defined as Either Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization	Number of participants that had first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization due to HF.	up to End of Study (78 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Month 12 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score	Change from baseline to Month 12 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	Baseline, Month 12
All Cause Death	Number of patients - All-cause death. All-cause death is common in Heart Failure HF patients this measures how many patients had this event.	up to end of study (78 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Wang GM, Li LJ, Tang WL, Wright JM. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD012569. doi: 10.1002/14651858.CD012569.pub2.
• Shen L, Claggett BL, Jhund PS, Abraham WT, Desai AS, Dickstein K, Gong J, Kober LV, Lefkowitz MP, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, McMurray JJV. Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE. Clin Res Cardiol. 2021 Aug;110(8):1334-1349. doi: 10.1007/s00392-021-01888-x. Epub 2021 Jun 8.
• Kristensen SL, Castagno D, Shen L, Jhund PS, Docherty KF, Rorth R, Abraham WT, Desai AS, Dickstein K, Rouleau JL, Zile MR, Swedberg K, Packer M, Solomon SD, Kober L, McMurray JJV; PARADIGM-HF and ATMOSPHERE Committees and Investigators.. Prevalence and incidence of intra-ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from PARADIGM-HF and ATMOSPHERE. Eur J Heart Fail. 2020 Dec;22(12):2370-2379. doi: 10.1002/ejhf.1972. Epub 2020 Sep 14.
• Docherty KF, Shen L, Castagno D, Petrie MC, Abraham WT, Bohm M, Desai AS, Dickstein K, Kober LV, Packer M, Rouleau JL, Solomon SD, Swedberg K, Vazir A, Zile MR, Jhund PS, McMurray JJV. Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction. Eur J Heart Fail. 2020 Mar;22(3):528-538. doi: 10.1002/ejhf.1682. Epub 2019 Dec 17.
• Dewan P, Rorth R, Raparelli V, Campbell RT, Shen L, Jhund PS, Petrie MC, Anand IS, Carson PE, Desai AS, Granger CB, Kober L, Komajda M, McKelvie RS, O'Meara E, Pfeffer MA, Pitt B, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Sex-Related Differences in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2019 Dec;12(12):e006539. doi: 10.1161/CIRCHEARTFAILURE.119.006539. Epub 2019 Dec 9. Erratum In: Circ Heart Fail. 2020 Jan;13(1):e000036.
• Shen L, Ramires F, Martinez F, Bodanese LC, Echeverria LE, Gomez EA, Abraham WT, Dickstein K, Kober L, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Jhund PS, Gimpelewicz CR, McMurray JJV; PARADIGM-HF and ATMOSPHERE Investigators and Committees. Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy. Circ Heart Fail. 2017 Nov;10(11):e004361. doi: 10.1161/CIRCHEARTFAILURE.117.004361.
• Kristensen SL, Jhund PS, Mogensen UM, Rorth R, Abraham WT, Desai A, Dickstein K, Rouleau JL, Zile MR, Swedberg K, Packer M, Solomon SD, Kober L, McMurray JJV; PARADIGM-HF and ATMOSPHERE Committees and Investigators. Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation. Circ Heart Fail. 2017 Oct;10(10):e004409. doi: 10.1161/CIRCHEARTFAILURE.117.004409.
• Kristensen SL, Mogensen UM, Tarnesby G, Gimpelewicz CR, Ali MA, Shao Q, Chiang Y, Jhund PS, Abraham WT, Dickstein K, McMurray JJV, Kober L. Aliskiren alone or in combination with enalapril vs. enalapril among patients with chronic heart failure with and without diabetes: a subgroup analysis from the ATMOSPHERE trial. Eur J Heart Fail. 2018 Jan;20(1):136-147. doi: 10.1002/ejhf.896. Epub 2017 Sep 25.
• McMurray JJ, Krum H, Abraham WT, Dickstein K, Kober LV, Desai AS, Solomon SD, Greenlaw N, Ali MA, Chiang Y, Shao Q, Tarnesby G, Massie BM; ATMOSPHERE Committees Investigators. Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure. N Engl J Med. 2016 Apr 21;374(16):1521-32. doi: 10.1056/NEJMoa1514859. Epub 2016 Apr 4.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Estimate): November 25, 2016
• Last Update Submitted That Met QC Criteria: October 3, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Heart Failure; eGFR; BNP; plasma renin activity; direct renin inhibitors; Cardiovascular death; KCCQ; outcome study; renin angiotensin aldosterone system; CHF hospitalization; morbi-mortality trial; endpoint driven; (NYHA class II to IV) with elevated; BNP and reduced LVEF
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Enalapril
• Other Study ID Numbers: CSPP100F2301; 2008-004104-31 (EudraCT Number)