Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF)

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction (PARAGON-HF)

The purpose of this study was to evaluate the effect of LCZ696 compared to valsartan in the reduction of cardiovascular death and heart failure(HF) hospitalizations in patients with HF with preserved ejection fraction.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: LCZ696; Drug: Valsartan

Detailed Description

This was a multicenter, randomized, double-blind, parallel group, active-controlled, study to evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan, on morbidity and mortality in heart failure patients (NYHA Class II-IV) with preserved ejection fraction. Specifically, the study evaluated the effect of sacubitril/valsartan compared to the active comparator valsartan in the reduction of the rate of CV death and total HF hospitalizations in patients with HFpEF. The trial consisted of two periods: (1) a single-blind treatment run-in epoch that lasted from 3 to 8 weeks, in which patients received valsartan 80 mg bid, followed by sacubitril/valsartan 100 mg bid and (2) a double-blind randomized treatment epoch (sacubitril/valsartan 200 mg bid or valsartan 160 mg bid). In this study, investigators were responsible for assessing and submitting all events which could potentially fulfill the criteria for the primary, secondary, or other clinical endpoints to a Clinical Endpoint Committee (CEC). Investigator reported events were assessed by the CEC for adjudication.

For angioedema or angioedema-like events, investigators completed an Adjudication Questionnaire for an Angioedema-like Event form. All angioedema reports were forwarded to an Angioedema Adjudication Committee (AAC) by Novartis for assessment.

• Study Type: Interventional
• Enrollment (Actual): 4822
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
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  • Buenos Aires, Argentina, C1425AGP
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  • Caba, Argentina, C1119ACN
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  • Cordoba, Argentina, X5022CPU
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  • Cordoba, Argentina, X5009BSN
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  • Cordoba, Argentina, X5000EVQ
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  • Cordoba, Argentina, X5016KET
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  • Cordoba, Argentina, X5000AAX
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  • Formosa, Argentina, P3600
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  • San Luis, Argentina, D5702JRS
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  • Santa Fe, Argentina, S3000FWO
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  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1280AEB
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    • Caba, Buenos Aires, Argentina, 1407
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    • Caba, Buenos Aires, Argentina, C1056ABJ
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    • Quilmes, Buenos Aires, Argentina, B1878GEG
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    • Ramos Mejia, Buenos Aires, Argentina, B1704ETD
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  • Capital Federal
    • Caba, Capital Federal, Argentina, C1179AAB
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  • Misiones
    • Posadas, Misiones, Argentina, N3300AHX
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  • Provincia De Salta
    • Ciudad de Salta, Provincia De Salta, Argentina, A4406BPF
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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, S2000DSV
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    • Rosario, Santa Fe, Argentina, 2000
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    • Rosario, Santa Fe, Argentina, S2000QID
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    • Rosario, Santa Fe, Argentina, 3080
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    • Geelong, Victoria, Australia, 3220
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• Israel
  • Hadera, Israel
    • Novartis Investigative Site
  • Hadera, Israel, 38100
    • Novartis Investigative Site
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Haifa, Israel, 3339419
    • Novartis Investigative Site
  • Lower Galilee, Israel, 15208
    • Novartis Investigative Site
  • Nahariya, Israel, 22100
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Rehovot, Israel, 76100
    • Novartis Investigative Site
  • Tel Giborim, Holon, Israel, 58100
    • Novartis Investigative Site
• Italy
  • Milano, Italy, 20149
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • AO
    • Aosta, AO, Italy, 11100
      • Novartis Investigative Site
  • AR
    • Cortona, AR, Italy, 52044
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
    • Treviglio, BG, Italy, 24047
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • IS
    • Pozzilli, IS, Italy, 86077
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • ME
    • Messina, ME, Italy, 98125
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Vimercate, MI, Italy, 200059
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06100
      • Novartis Investigative Site
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RM
    • Ariccia, RM, Italy, 00041
      • Novartis Investigative Site
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
    • Roma, RM, Italy, 00163
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34149
      • Novartis Investigative Site
    • Trieste, TS, Italy, 34142
      • Novartis Investigative Site
  • UD
    • Palmanova, UD, Italy, 33057
      • Novartis Investigative Site
    • San Daniele Del Friuli, UD, Italy, 33038
      • Novartis Investigative Site
  • VE
    • Venezia, VE, Italy, 30174
      • Novartis Investigative Site
  • Va
    • Saronno, Va, Italy, 21047
      • Novartis Investigative Site
• Japan
  • Aichi
    • Seto-city, Aichi, Japan, 489-8642
      • Novartis Investigative Site
  • Fukuka
    • Chikushino-city, Fukuka, Japan, 818-8516
      • Novartis Investigative Site
  • Gifu
    • Ogaki-city, Gifu, Japan, 503-8502
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hyogo
    • Amagasaki city, Hyogo, Japan, 660 8550
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920 8650
      • Novartis Investigative Site
  • Iwate
    • Morioka, Iwate, Japan, 020 0066
      • Novartis Investigative Site
  • Kagawa
    • Kanonji-city, Kagawa, Japan, 769-1695
      • Novartis Investigative Site
    • Takamatsu city, Kagawa, Japan, 760 8557
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 236 0051
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 227-8501
      • Novartis Investigative Site
  • Miyagi
    • Sendai city, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
  • Nara
    • Kashihara city, Nara, Japan, 634 8522
      • Novartis Investigative Site
  • Saitama
    • Sayama-city, Saitama, Japan, 350-1305
      • Novartis Investigative Site
  • Shiga
    • Kusatsu city, Shiga, Japan, 525 8585
      • Novartis Investigative Site
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8309
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 142-8666
      • Novartis Investigative Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 705 718
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 02841
    • Novartis Investigative Site
  • Bucheon Si
    • Gyeonggi do, Bucheon Si, Korea, Republic of, 422-711
      • Novartis Investigative Site
  • Chungcheongbuk Do
    • Cheongju si, Chungcheongbuk Do, Korea, Republic of, 28644
      • Novartis Investigative Site
  • Gangwon-do
    • Wonju, Gangwon-do, Korea, Republic of, 26427
      • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • KOR
    • Incheon, KOR, Korea, Republic of, 22332
      • Novartis Investigative Site
    • Seoul, KOR, Korea, Republic of, 08308
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Novartis Investigative Site
  • Queretaro, Mexico, 76000
    • Novartis Investigative Site
  • San Luis Potosi, Mexico, 78200
    • Novartis Investigative Site
  • San Luis Potosí, Mexico, 78200
    • Novartis Investigative Site
  • Coahulia
    • Torreon, Coahulia, Mexico, 27000
      • Novartis Investigative Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14080
      • Novartis Investigative Site
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37530
      • Novartis Investigative Site
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45200
      • Novartis Investigative Site
  • Queretaro
    • San Juan del Rio, Queretaro, Mexico, 76800
      • Novartis Investigative Site
  • San Luis Potosí
    • San Luis Potosi, San Luis Potosí, Mexico, 78240
      • Novartis Investigative Site
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80230
      • Novartis Investigative Site
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Novartis Investigative Site
  • Blaricum, Netherlands, 1261 AN
    • Novartis Investigative Site
  • Den Haag, Netherlands, 2512 VA
    • Novartis Investigative Site
  • Ede, Netherlands, 6716 RP
    • Novartis Investigative Site
  • Gouda, Netherlands, 2803 HH
    • Novartis Investigative Site
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • Hardenberg, Netherlands, 7770 AA
    • Novartis Investigative Site
  • Harderwijk, Netherlands, 3840 AC
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6500 HB
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3015 CE
    • Novartis Investigative Site
  • Sneek, Netherlands, 8601 ZK
    • Novartis Investigative Site
  • Tilburg, Netherlands, 5022 GC
    • Novartis Investigative Site
  • DZ
    • Apeldoorn, DZ, Netherlands, 7334
      • Novartis Investigative Site
  • NL
    • Den Haag, NL, Netherlands, 2597 AX
      • Novartis Investigative Site
  • PP
    • Almelo, PP, Netherlands, 7609
      • Novartis Investigative Site
• Norway
  • Loerenskog, Norway, NO 1478
    • Novartis Investigative Site
  • Oslo, Norway, 0450
    • Novartis Investigative Site
  • Stavanger, Norway, 4068
    • Novartis Investigative Site
  • Tromsoe, Norway, NO-9038
    • Novartis Investigative Site
• Peru
  • 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 Isidro, Lima, Peru, 27
      • Novartis Investigative Site
• Philippines
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Novartis Investigative Site
  • Manila
    • Quezon City, Manila, Philippines, 1100
      • Novartis Investigative Site
• Poland
  • Gdynia, Poland, 81-157
    • Novartis Investigative Site
  • Gdynia, Poland, 81-548
    • Novartis Investigative Site
  • Grodzisk Mazowiecki, Poland, 05 825
    • Novartis Investigative Site
  • Katowice, Poland, 40-645
    • Novartis Investigative Site
  • Krakow, Poland, 31 501
    • Novartis Investigative Site
  • Krakow, Poland, 30-015
    • Novartis Investigative Site
  • Lublin, Poland, 20-363
    • Novartis Investigative Site
  • Sandomierz, Poland, 27 600
    • Novartis Investigative Site
  • Staszów, Poland, 28-200
    • Novartis Investigative Site
  • Torun, Poland, 87-100
    • Novartis Investigative Site
  • Warszawa, Poland, 02-097
    • Novartis Investigative Site
  • Warszawa, Poland, 04-154
    • Novartis Investigative Site
  • Warszawa/Anin, Poland, 04-761
    • Novartis Investigative Site
  • Zabrze, Poland, 41 800
    • Novartis Investigative Site
  • Zamosc, Poland, 22-400
    • Novartis Investigative Site
  • Lodzkie
    • Lodz, Lodzkie, Poland, 90 549
      • Novartis Investigative Site
• Romania
  • Arad, Romania, 310158
    • Novartis Investigative Site
  • Baia Mare, Romania, 430222
    • Novartis Investigative Site
  • Bucharest, Romania, 050098
    • Novartis Investigative Site
  • Bucuresti, Romania, 062272
    • Novartis Investigative Site
  • Targu Mures, Romania, 540142
    • Novartis Investigative Site
  • Targu Mures, Romania, 540143
    • Novartis Investigative Site
  • Timisoara, Romania, 300041
    • Novartis Investigative Site
  • Arges
    • Pitesti, Arges, Romania, 110438
      • Novartis Investigative Site
  • District 1
    • Bucuresti, District 1, Romania, 014461
      • Novartis Investigative Site
  • Jud. Dolj
    • Craiova, Jud. Dolj, Romania, 200497
      • Novartis Investigative Site
  • Jud. Iasi
    • Sibiu, Jud. Iasi, Romania, 550371
      • Novartis Investigative Site
  • Timis
    • Timisoara, Timis, Romania, 300362
      • Novartis Investigative Site
    • Timisoara, Timis, Romania, 300125
      • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation, 620137
    • Novartis Investigative Site
  • Ivanovo, Russian Federation, 153012
    • Novartis Investigative Site
  • Izhevsk, Russian Federation, 426009
    • Novartis Investigative Site
  • Izhevsk, Russian Federation, 426063
    • Novartis Investigative Site
  • Kemerovo, Russian Federation, 650029
    • Novartis Investigative Site
  • Kemerovo, Russian Federation, 650099
    • Novartis Investigative Site
  • Kirov, Russian Federation, 610035
    • Novartis Investigative Site
  • Kirov, Russian Federation, 610027
    • Novartis Investigative Site
  • Moscow, Russian Federation, 117198
    • Novartis Investigative Site
  • Moscow, Russian Federation, 121552
    • Novartis Investigative Site
  • Moscow, Russian Federation, 121309
    • Novartis Investigative Site
  • Moscow, Russian Federation, 101990
    • Novartis Investigative Site
  • N.Novgorod, Russian Federation, 603005
    • Novartis Investigative Site
  • Perm, Russian Federation, 614990
    • Novartis Investigative Site
  • Rostov on Don, Russian Federation, 344022
    • Novartis Investigative Site
  • Rostov-on-Don, Russian Federation, 344068
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 199106
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 192257
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • Sestroretsk, Russian Federation, 197706
    • Novartis Investigative Site
  • Smolensk, Russian Federation, 214018
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 196601
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 194295
    • Novartis Investigative Site
  • St.- Petersburg, Russian Federation, 197110
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novartis Investigative Site
  • Beograd, Serbia, 11040
    • Novartis Investigative Site
  • Nis, Serbia, 18000
    • Novartis Investigative Site
  • Niska Banja, Serbia, 18205
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 529889
    • Novartis Investigative Site
  • Singapore, Singapore, 308433
    • Novartis Investigative Site
  • Singapore, Singapore, 169609
    • Novartis Investigative Site
  • Singapore, Singapore, 768828
    • Novartis Investigative Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Novartis Investigative Site
  • Bratislava, Slovakia, 833 48
    • Novartis Investigative Site
  • Bratislava, Slovakia, 821 07
    • Novartis Investigative Site
  • Bratislava, Slovakia, 842 31
    • Novartis Investigative Site
  • Bratislava, Slovakia, 841 07
    • Novartis Investigative Site
  • Bratislava, Slovakia, 831 01
    • Novartis Investigative Site
  • Bratislava, Slovakia, 851 01
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 01
    • Novartis Investigative Site
  • Levice, Slovakia, 934 01
    • Novartis Investigative Site
  • Lucenec, Slovakia, 98439
    • Novartis Investigative Site
  • Lucenec, Slovakia, 984 01
    • Novartis Investigative Site
  • Nitra, Slovakia, 949 01
    • Novartis Investigative Site
  • Nitra, Slovakia, 949 88
    • Novartis Investigative Site
  • Nove Zamky, Slovakia, 940 01
    • Novartis Investigative Site
  • Nove Zamky, Slovakia, 94002
    • Novartis Investigative Site
  • Piestany, Slovakia, 921 01
    • Novartis Investigative Site
  • Presov, Slovakia, 080 01
    • Novartis Investigative Site
  • Svidnik, Slovakia, 089 01
    • Novartis Investigative Site
  • Trebisov, Slovakia, 075 01
    • Novartis Investigative Site
  • Zilina, Slovakia, 012 07
    • Novartis Investigative Site
  • Slovak Republic
    • Brezno, Slovak Republic, Slovakia, 977 42
      • Novartis Investigative Site
    • Komarno, Slovak Republic, Slovakia, 94501
      • Novartis Investigative Site
    • Levice, Slovak Republic, Slovakia, 93401
      • Novartis Investigative Site
    • Namestovo, Slovak Republic, Slovakia, 02901
      • Novartis Investigative Site
    • Povazska Bystrica, Slovak Republic, Slovakia, 01701
      • Novartis Investigative Site
    • Presov, Slovak Republic, Slovakia, 08001
      • Novartis Investigative Site
• Slovenia
  • Golnik, Slovenia, 4204
    • Novartis Investigative Site
  • Ljubljana, Slovenia, 1000
    • Novartis Investigative Site
• South Africa
  • Alberton, South Africa, 1449
    • Novartis Investigative Site
  • Bloemfontein, South Africa, 9301
    • Novartis Investigative Site
  • Cape Town, South Africa, 7500
    • Novartis Investigative Site
  • Cape Town, South Africa, 7531
    • Novartis Investigative Site
  • Cape Town, South Africa, 7925
    • Novartis Investigative Site
  • Durban, South Africa, 4001
    • Novartis Investigative Site
  • Tongaat, South Africa, 3300
    • Novartis Investigative Site
  • Western Cape, South Africa, 7130
    • Novartis Investigative Site
  • Worcester, South Africa, 6850
    • Novartis Investigative Site
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Novartis Investigative Site
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Novartis Investigative Site
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa, 4052
      • Novartis Investigative Site
• Spain
  • Ciudad Real, Spain, 13005
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Andalucia
    • Almeria, Andalucia, Spain, 04120
      • Novartis Investigative Site
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Marbella, Andalucia, Spain, 29600
      • Novartis Investigative Site
    • Sanlúcar de Barrameda, Andalucia, Spain, 11540
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Barcelona
    • Sant Joan Despi, Barcelona, Spain, 08970
      • Novartis Investigative Site
  • Cadiz
    • Villamartin, Cadiz, Spain, 11650
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Castilla Y Leon
    • Aranda de Duero, Castilla Y Leon, Spain, 09400
      • Novartis Investigative Site
    • Leon, Castilla Y Leon, Spain, 24071
      • Novartis Investigative Site
  • Cataluna
    • Lerida, Cataluna, Spain, 25198
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alzira, Comunidad Valenciana, Spain, 46600
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Extremadura
    • Merida, Extremadura, Spain, 06800
      • Novartis Investigative Site
  • Galicia
    • A Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Girona
    • Olot, Girona, Spain, 17800
      • Novartis Investigative Site
  • Madrid
    • Mostoles, Madrid, Spain, 28935
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
• Sweden
  • Danderyd, Sweden, 182 88
    • Novartis Investigative Site
  • Falun, Sweden, 791 82
    • Novartis Investigative Site
  • Goteborg, Sweden, 413 45
    • Novartis Investigative Site
  • Karlstad, Sweden, 652 30
    • Novartis Investigative Site
  • Lund, Sweden, 222 21
    • Novartis Investigative Site
  • Orebro, Sweden, 701 85
    • Novartis Investigative Site
  • Stockholm, Sweden, 17176
    • Novartis Investigative Site
  • Vasteras, Sweden, 72189
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Biel, Switzerland, 2502
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Changhua, Taiwan, 50006
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 80756
    • Novartis Investigative Site
  • New Taipei, Taiwan, 22060
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Tainan, Taiwan, 71004
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Yilan, Taiwan, 26058
    • Novartis Investigative Site
  • Taiwan ROC
    • Tainan, Taiwan ROC, Taiwan, 70403
      • Novartis Investigative Site
• Turkey
  • Haydarpasa Istanbul, Turkey, 34668
    • Novartis Investigative Site
  • Istanbul, Turkey, 34304
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Novartis Investigative Site
  • Pendik / Istanbul, Turkey, 34899
    • Novartis Investigative Site
  • Sivas, Turkey, 58140
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • Cheshire, United Kingdom, CW1 4QJ
    • Novartis Investigative Site
  • Coventry, United Kingdom, CV2 2DX
    • Novartis Investigative Site
  • Dundee, United Kingdom, DD1 9SY
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G20 0XA
    • Novartis Investigative Site
  • Hull, United Kingdom, HU16 5JQ
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • London, United Kingdom, SW 6NP
    • Novartis Investigative Site
  • Newport, United Kingdom, NP20 2UB
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Sheffield, United Kingdom, S5 7AU
    • Novartis Investigative Site
  • Swindon, United Kingdom, SN3 6BB
    • Novartis Investigative Site
  • Wiltshire, United Kingdom, SN15 2SB
    • Novartis Investigative Site
  • Wrexham, United Kingdom, LL13 7TD
    • Novartis Investigative Site
  • Buckinghamshire
    • High Wycombe, Buckinghamshire, United Kingdom, HP11 2TT
      • Novartis Investigative Site
  • Cleveland
    • Stockton on Tees, Cleveland, United Kingdom, TS19 8PE
      • Novartis Investigative Site
  • Co Durham
    • Darlington, Co Durham, United Kingdom, DL3 8SQ
      • Novartis Investigative Site
  • County Durham
    • Durham, County Durham, United Kingdom, DH1 5TW
      • Novartis Investigative Site
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Novartis Investigative Site
  • Dorset
    • Dorchester, Dorset, United Kingdom, DT1 2JY
      • Novartis Investigative Site
  • GBR
    • Peterborough, GBR, United Kingdom, PE3 6DA
      • Novartis Investigative Site
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Novartis Investigative Site
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Novartis Investigative Site
  • Lancashire
    • Oldham, Lancashire, United Kingdom, OL1 2JH
      • Novartis Investigative Site
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Novartis Investigative Site
  • Nothern Ireland
    • Portadown, Nothern Ireland, United Kingdom, BT63 5QQ
      • Novartis Investigative Site
  • Peterborough
    • Wansford, Peterborough, United Kingdom, PE8 6PL
      • Novartis Investigative Site
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 8TA
      • Novartis Investigative Site
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Novartis Investigative Site
  • Tyne And Wear
    • Gateshead, Tyne And Wear, United Kingdom, NE9 6SX
      • Novartis Investigative Site
  • West Dumbartonshire
    • Clydebank, West Dumbartonshire, United Kingdom, G81 4HX
      • Novartis Investigative Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Left ventricular ejection fraction (LVEF) ≥45% by echo during screening epoch or within 6 months prior to study entry.
• Symptom(s) of heart failure (HF) and requiring treatment with diuretic(s) for HF at least 30 days prior to study entry.
• Current symptom(s) of HF (NYHA class II-IV)
• Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram.
• Elevated NT-proBNP

Exclusion Criteria:

• Any prior measurement of LVEF < 40%.
• Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention within 3 months or and elective PCI within 30 days prior to entry.
• Any clinical event within the 6 months prior to entry could have reduced the LVEF (e.g., MI, CABG), unless an echo measurement performed after the event confirms a LVEF ≥45%.
• Current acute decompensated HF requiring therapy.
• Patients who require treatment with 2 or more of the following: an angiotensin converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB) or a renin inhibitor.
• Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.
• Systolic blood pressure (SBP) ≥ 180 mmHg at entry, or SBP >150 mmHg and <180 mmHg at entry unless the patient is receiving 3 or more antihypertensive drugs, or SBP < 110 mmHg at entry.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696; Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of LCZ696 during the double blind period is 200 mg b.i.d.	Drug: LCZ696; LCZ696 50mg, 100mg and 200 mg dosage strengths will be available for dose adjustments.
Active Comparator: Valsartan; Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of Valsartan during the double blind period is 160 mg b.i.d.	Drug: Valsartan; Valsartan 40mg, 80mg and 160mg dosage strengths will be available for dose adjustments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Number of Primary Composite Events of Cardiovascular (CV) Death and Total (First and Recurrent) HF Hospitalizations.	The primary objective of this study is to compare LCZ696 to valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations, in HF patients (New York Heart Association [NYHA] Class II-IV) with preserved ejection fraction (left ventricular ejection fraction [LVEF] ≥45%). The treatment arm with the lower rate of events will be deemed as having a successful response.	Total follow up time (up to 57 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Clinical Summary Score From Baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ)	The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure (HF) patients. The clinical summary score, which is derived from the physical limitations and heart failure (HF) symptoms domains of the KCCQ is a valid measure for assessing the patient's health aspects that may be influenced by CV medications. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. Evaluation of change from baseline to month 8 in KCCQ a most sensitive, specific, and responsive health-related quality of life measure for heart failure symptoms and physical limitations.	Baseline, 8 months
Change From Baseline to Month 8 in New York Heart Association (NYHA) Functional Class	Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a heart failure's (HF) patients' level of functionality based on the signs and symptoms of HF exhibited by the patient.	Baseline, 8 months
Participants With First Occurrence of a Composite Renal Endpoint	Analyis of composite renal endpoint defined as renal death, or reaching ESRD, or ≥50% decline in eGFR relative to baseline, using Cox's proportional hazards model.	Randomization to total follow-up time (up to 57 months)
All-cause Mortality	Analysis for all-cause mortality using Cox's proportional hazards model.	Randomization to total follow up time (up to 57 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Butt JH, Dewan P, Jhund PS, Anand IS, Atar D, Ge J, Desai AS, Echeverria LE, Kober L, Lam CSP, Maggioni AP, Martinez F, Packer M, Rouleau JL, Sim D, Van Veldhuisen DJ, Vrtovec B, Zannad F, Zile MR, Gong J, Lefkowitz MP, Rizkala AR, Solomon SD, McMurray JJV. Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction. J Am Coll Cardiol. 2022 Sep 20;80(12):1130-1143. doi: 10.1016/j.jacc.2022.06.037. Epub 2022 Aug 29.
• Wijkman MO, Claggett B, Vaduganathan M, Cunningham JW, Rørth R, Jackson A, Packer M, Zile M, Rouleau J, Swedberg K, Lefkowitz M, Shah SJ, Pfeffer MA, McMurray JJV, Solomon SD. Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials. Cardiovasc Diabetol. 2022 Jun 18;21(1):110. doi: 10.1186/s12933-022-01545-1.
• Vaduganathan M, Claggett BL, Inciardi RM, Fonarow GC, McMurray JJV, Solomon SD. Estimating the Benefits of Combination Medical Therapy in Heart Failure With Mildly Reduced and Preserved Ejection Fraction. Circulation. 2022 Jun 7;145(23):1741-1743. doi: 10.1161/CIRCULATIONAHA.121.058929. Epub 2022 May 23. No abstract available.
• Vaduganathan M, Claggett BL, McMurray JJV, Solomon SD. Health Status Trajectories Before and After Hospitalization for Heart Failure. Circulation. 2022 Jun 21;145(25):1872-1874. doi: 10.1161/CIRCULATIONAHA.122.059282. Epub 2022 May 21. No abstract available.
• Cikes M, Planinc I, Claggett B, Cunningham J, Milicic D, Sweitzer N, Senni M, Gori M, Linssen G, Shah SJ, Packer M, Pfeffer M, Zile MR, Anand I, Chiang LM, Lam CSP, Redfield M, Desai AS, McMurray JJV, Solomon SD. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. JACC Heart Fail. 2022 May;10(5):336-346. doi: 10.1016/j.jchf.2022.01.018. Epub 2022 Apr 6.
• Jackson AM, Rorth R, Liu J, Kristensen SL, Anand IS, Claggett BL, Cleland JGF, Chopra VK, Desai AS, Ge J, Gong J, Lam CSP, Lefkowitz MP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rizkala AR, Rouleau JL, Seferovic PM, Tromp J, Van Veldhuisen DJ, Yilmaz MB, Zannad F, Zile MR, Kober L, Petrie MC, Jhund PS, Solomon SD, McMurray JJV; PARAGON-HF Committees and Investigators. Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2022 Mar;24(3):497-509. doi: 10.1002/ejhf.2403. Epub 2022 Jan 4.
• Desai AS, Vaduganathan M, Cleland JG, Claggett BL, Barkoudah E, Finn P, McCausland FR, Yilmaz MB, Lefkowitz M, Shi V, Pfeffer MA, McMurray JJV, Solomon SD. Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial. Circ Heart Fail. 2021 Dec;14(12):e008597. doi: 10.1161/CIRCHEARTFAILURE.121.008597. Epub 2021 Nov 22.
• Mooney L, Hawkins NM, Jhund PS, Redfield MM, Vaduganathan M, Desai AS, Rouleau JL, Minamisawa M, Shah AM, Lefkowitz MP, Zile MR, Van Veldhuisen DJ, Pfeffer MA, Anand IS, Maggioni AP, Senni M, Claggett BL, Solomon SD, McMurray JJV. Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON-HF. J Am Heart Assoc. 2021 Dec 7;10(23):e021494. doi: 10.1161/JAHA.121.021494. Epub 2021 Nov 19.
• Jackson AM, Jhund PS, Anand IS, Dungen HD, Lam CSP, Lefkowitz MP, Linssen G, Lund LH, Maggioni AP, Pfeffer MA, Rouleau JL, Saraiva JFK, Senni M, Vardeny O, Wijkman MO, Yilmaz MB, Saito Y, Zile MR, Solomon SD, McMurray JJV. Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction. Eur Heart J. 2021 Sep 21;42(36):3741-3752. doi: 10.1093/eurheartj/ehab499.
• Felker GM, Butler J, Januzzi JL Jr, Desai AS, McMurray JJV, Solomon SD. Probabilistic Readjudication of Heart Failure Hospitalization Events in the PARAGON-HF Study. Circulation. 2021 Jun 8;143(23):2316-2318. doi: 10.1161/CIRCULATIONAHA.121.054496. Epub 2021 Jun 7. No abstract available.
• Selvaraj S, Claggett BL, Packer M, Zannad F, Anand IS, Pieske B, Zhao Z, Shi VC, Lefkowitz MP, McMurray JJV, Solomon SD. Effects of Sacubitril/Valsartan on Serum Lipids in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2021 Sep 7;10(17):e022069. doi: 10.1161/JAHA.121.022069. Epub 2021 May 16.
• Shen L, Jhund PS, Anand IS, Bhatt AS, Desai AS, Maggioni AP, Martinez FA, Pfeffer MA, Rizkala AR, Rouleau JL, Swedberg K, Vaduganathan M, Vardeny O, van Veldhuisen DJ, Zannad F, Zile MR, Packer M, Solomon SD, McMurray JJV. Incidence and Outcomes of Pneumonia in Patients With Heart Failure. J Am Coll Cardiol. 2021 Apr 27;77(16):1961-1973. doi: 10.1016/j.jacc.2021.03.001.
• Tromp J, Claggett BL, Liu J, Jackson AM, Jhund PS, Kober L, Widimsky J, Boytsov SA, Chopra VK, Anand IS, Ge J, Chen CH, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Rizkala AR, Inubushi-Molessa A, Lefkowitz MP, Shi VC, McMurray JJV, Solomon SD, Lam CSP; PARAGON-HF Investigators. Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. Circ Heart Fail. 2021 Apr;14(4):e007901. doi: 10.1161/CIRCHEARTFAILURE.120.007901. Epub 2021 Apr 19.
• Vaduganathan M, Cunningham JW, Claggett BL, Causland FM, Barkoudah E, Finn P, Zannad F, Pfeffer MA, Rizkala AR, Sabarwal S, McMurray JJV, Solomon S, Desai AS. Worsening Heart Failure Episodes Outside a Hospital Setting in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. JACC Heart Fail. 2021 May;9(5):374-382. doi: 10.1016/j.jchf.2021.01.014. Epub 2021 Apr 7.
• Gronda E, Vanoli E, Iacoviello M. The PARAGON-HF trial: the sacubitril/valsartan in heart failure with preserved ejection fraction. Eur Heart J Suppl. 2020 Nov 18;22(Suppl L):L77-L81. doi: 10.1093/eurheartj/suaa140. eCollection 2020 Nov.
• Jering K, Claggett B, Redfield MM, Shah SJ, Anand IS, Martinez F, Sabarwal SV, Seferovic PM, Kerr Saraiva JF, Katova T, Lefkowitz MP, Pfeffer MA, McMurray JJV, Solomon SD. Burden of Heart Failure Signs and Symptoms, Prognosis, and Response to Therapy: The PARAGON-HF Trial. JACC Heart Fail. 2021 May;9(5):386-397. doi: 10.1016/j.jchf.2021.01.011. Epub 2021 Mar 10.
• Jering KS, Zannad F, Claggett B, Mc Causland FR, Ferreira JP, Desai A, Barkoudah E, McMurray JJV, Pfeffer MA, Solomon SD. Cardiovascular and Renal Outcomes of Mineralocorticoid Receptor Antagonist Use in PARAGON-HF. JACC Heart Fail. 2021 Jan;9(1):13-24. doi: 10.1016/j.jchf.2020.08.014. Epub 2020 Nov 11.
• Mc Causland FR, Lefkowitz MP, Claggett B, Anavekar NS, Senni M, Gori M, Jhund PS, McGrath MM, Packer M, Shi V, Van Veldhuisen DJ, Zannad F, Comin-Colet J, Pfeffer MA, McMurray JJV, Solomon SD. Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction. Circulation. 2020 Sep 29;142(13):1236-1245. doi: 10.1161/CIRCULATIONAHA.120.047643. Epub 2020 Aug 17.
• Cunningham JW, Claggett BL, O'Meara E, Prescott MF, Pfeffer MA, Shah SJ, Redfield MM, Zannad F, Chiang LM, Rizkala AR, Shi VC, Lefkowitz MP, Rouleau J, McMurray JJV, Solomon SD, Zile MR. Effect of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFpEF. J Am Coll Cardiol. 2020 Aug 4;76(5):503-514. doi: 10.1016/j.jacc.2020.05.072.
• Cunningham JW, Vaduganathan M, Claggett BL, Zile MR, Anand IS, Packer M, Zannad F, Lam CSP, Janssens S, Jhund PS, Kober L, Rouleau J, Shah SJ, Chopra VK, Shi VC, Lefkowitz MP, Prescott MF, Pfeffer MA, McMurray JJV, Solomon SD. Effects of Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2020 May;8(5):372-381. doi: 10.1016/j.jchf.2020.03.002. Epub 2020 Mar 30.
• Selvaraj S, Claggett BL, Bohm M, Anker SD, Vaduganathan M, Zannad F, Pieske B, Lam CSP, Anand IS, Shi VC, Lefkowitz MP, McMurray JJV, Solomon SD. Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan. J Am Coll Cardiol. 2020 Apr 14;75(14):1644-1656. doi: 10.1016/j.jacc.2020.02.009. Epub 2020 Mar 16.
• Shah AM, Cikes M, Prasad N, Li G, Getchevski S, Claggett B, Rizkala A, Lukashevich I, O'Meara E, Ryan JJ, Shah SJ, Mullens W, Zile MR, Lam CSP, McMurray JJV, Solomon SD; PARAGON-HF Investigators. Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. J Am Coll Cardiol. 2019 Dec 10;74(23):2858-2873. doi: 10.1016/j.jacc.2019.09.063.
• Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K, Rouleau J, A Pfeffer M, Desai A, Lund LH, Kober L, Anand I, Sweitzer N, Linssen G, Merkely B, Luis Arango J, Vinereanu D, Chen CH, Senni M, Sibulo A, Boytsov S, Shi V, Rizkala A, Lefkowitz M, McMurray JJV. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. Circulation. 2020 Feb 4;141(5):352-361. doi: 10.1161/CIRCULATIONAHA.119.044586. Epub 2019 Nov 17.
• McMurray JJV, Jackson AM, Lam CSP, Redfield MM, Anand IS, Ge J, Lefkowitz MP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Rizkala AR, Sabarwal SV, Shah AM, Shah SJ, Shi VC, van Veldhuisen DJ, Zannad F, Zile MR, Cikes M, Goncalvesova E, Katova T, Kosztin A, Lelonek M, Sweitzer N, Vardeny O, Claggett B, Jhund PS, Solomon SD. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF. Circulation. 2020 Feb 4;141(5):338-351. doi: 10.1161/CIRCULATIONAHA.119.044491. Epub 2019 Nov 17.
• Vaduganathan M, Claggett BL, Desai AS, Anker SD, Perrone SV, Janssens S, Milicic D, Arango JL, Packer M, Shi VC, Lefkowitz MP, McMurray JJV, Solomon SD. Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared With Valsartan in HFpEF. J Am Coll Cardiol. 2020 Jan 28;75(3):245-254. doi: 10.1016/j.jacc.2019.11.003. Epub 2019 Nov 11.
• Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
• Chandra A, Vaduganathan M, Lewis EF, Claggett BL, Rizkala AR, Wang W, Lefkowitz MP, Shi VC, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, McMurray JJV, Solomon SD; PARAGON-HF Investigators. Health-Related Quality of Life in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. JACC Heart Fail. 2019 Oct;7(10):862-874. doi: 10.1016/j.jchf.2019.05.015. Epub 2019 Jul 10.
• Solomon SD, Rizkala AR, Lefkowitz MP, Shi VC, Gong J, Anavekar N, Anker SD, Arango JL, Arenas JL, Atar D, Ben-Gal T, Boytsov SA, Chen CH, Chopra VK, Cleland J, Comin-Colet J, Duengen HD, Echeverria Correa LE, Filippatos G, Flammer AJ, Galinier M, Godoy A, Goncalvesova E, Janssens S, Katova T, Kober L, Lelonek M, Linssen G, Lund LH, O'Meara E, Merkely B, Milicic D, Oh BH, Perrone SV, Ranjith N, Saito Y, Saraiva JF, Shah S, Seferovic PM, Senni M, Sibulo AS Jr, Sim D, Sweitzer NK, Taurio J, Vinereanu D, Vrtovec B, Widimsky J Jr, Yilmaz MB, Zhou J, Zweiker R, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, McMurray JJV. Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial. Circ Heart Fail. 2018 Jul;11(7):e004962. doi: 10.1161/CIRCHEARTFAILURE.118.004962.
• Mutze T, Glimm E, Schmidli H, Friede T. Group sequential designs with robust semiparametric recurrent event models. Stat Methods Med Res. 2019 Aug;28(8):2385-2403. doi: 10.1177/0962280218780538. Epub 2018 Jun 11.
• Solomon SD, Rizkala AR, Gong J, Wang W, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Shi VC, Lefkowitz MP, McMurray JJV. Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial. JACC Heart Fail. 2017 Jul;5(7):471-482. doi: 10.1016/j.jchf.2017.04.013. Epub 2017 Jun 26.
• Rossi A, Gheorghiade M, Triposkiadis F, Solomon SD, Pieske B, Butler J. Left atrium in heart failure with preserved ejection fraction: structure, function, and significance. Circ Heart Fail. 2014 Nov;7(6):1042-9. doi: 10.1161/CIRCHEARTFAILURE.114.001276. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2014
• Primary Completion (Actual): June 7, 2019
• Study Completion (Actual): June 7, 2019

Study Registration Dates

• First Submitted: August 8, 2013
• First Submitted That Met QC Criteria: August 8, 2013
• First Posted (Estimate): August 12, 2013

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Heart failure; diastolic heart failure; preserved ejection fraction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696D2301; 2013-001747-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No