- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02884206
Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction (PERSPECTIVE)
A Multicenter, Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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ARG
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Buenos Aires, ARG, Argentina, C1405BCK
- Novartis Investigative Site
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Buenos Aires
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Caba, Buenos Aires, Argentina, 1407
- Novartis Investigative Site
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Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1119ACN
- Novartis Investigative Site
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Ramos Mejia, Buenos Aires, Argentina, B1704ETD
- Novartis Investigative Site
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Capital Federal
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Caba, Capital Federal, Argentina, C1179AAB
- Novartis Investigative Site
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Queensland
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Chemside, Queensland, Australia, 4032
- Novartis Investigative Site
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Milton, Queensland, Australia, 4064
- Novartis Investigative Site
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South Australia
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Bedford Park, South Australia, Australia, 5042
- Novartis Investigative Site
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Victoria
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Geelong, Victoria, Australia, 3220
- Novartis Investigative Site
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Aalst, Belgium, 9300
- Novartis Investigative Site
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Sofia, Bulgaria, 1431
- Novartis Investigative Site
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BGR
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Sofia, BGR, Bulgaria, 1407
- Novartis Investigative Site
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Ontario
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Hamilton, Ontario, Canada, L8L 2X2
- Novartis Investigative Site
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Quebec
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Greenfield Park, Quebec, Canada, J4V 2G8
- Novartis Investigative Site
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Rijeka, Croatia, 51000
- Novartis Investigative Site
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Zagreb, Croatia, 10000
- Novartis Investigative Site
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Paris, France, 75013
- Novartis Investigative Site
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Tourcoing, France, 59208
- Novartis Investigative Site
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Berlin, Germany, 10367
- Novartis Investigative Site
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Berlin, Germany, 13353
- Novartis Investigative Site
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Berlin Buch, Germany, 13125
- Novartis Investigative Site
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Bielefeld, Germany, 33604
- Novartis Investigative Site
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Bitburg, Germany, 54634
- Novartis Investigative Site
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Dessau-Roßlau, Germany, 06846
- Novartis Investigative Site
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Dresden, Germany, 01277
- Novartis Investigative Site
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Elsterwerda, Germany, 04910
- Novartis Investigative Site
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Frankfurt, Germany, 60594
- Novartis Investigative Site
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Koeln, Germany, 50937
- Novartis Investigative Site
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Koeln, Germany, 51065
- Novartis Investigative Site
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Ulm, Germany, 89077
- Novartis Investigative Site
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Wuerzburg, Germany, 97080
- Novartis Investigative Site
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Wuppertal, Germany, 42109
- Novartis Investigative Site
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Bavaria
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Regensburg, Bavaria, Germany, 93053
- Novartis Investigative Site
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Sachsen
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Dresden, Sachsen, Germany, 01099
- Novartis Investigative Site
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AN
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Ancona, AN, Italy, 60128
- Novartis Investigative Site
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BG
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Bergamo, BG, Italy, 24127
- Novartis Investigative Site
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FE
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Cona, FE, Italy, 44100
- Novartis Investigative Site
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FI
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Firenze, FI, Italy, 50134
- Novartis Investigative Site
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IS
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Pozzilli, IS, Italy, 86077
- Novartis Investigative Site
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MI
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Rozzano, MI, Italy, 20089
- Novartis Investigative Site
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MO
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Modena, MO, Italy, 41100
- Novartis Investigative Site
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PI
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Pisa, PI, Italy, 56124
- Novartis Investigative Site
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Gangwon-Do
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Wonju, Gangwon-Do, Korea, Republic of, 26426
- Novartis Investigative Site
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Gyeonggi Do
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Seongnam Si, Gyeonggi Do, Korea, Republic of, 13620
- Novartis Investigative Site
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Korea
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Seoul, Korea, Korea, Republic of, 03080
- Novartis Investigative Site
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Vilnius, Lithuania, LT-08661
- Novartis Investigative Site
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LTU
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Kaunas, LTU, Lithuania, LT 50161
- Novartis Investigative Site
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Amsterdam, Netherlands, 1081 HV
- Novartis Investigative Site
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Hertogenbosch, Netherlands, 5200
- Novartis Investigative Site
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Bialystok, Poland, 15 276
- Novartis Investigative Site
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Katowice, Poland, 40-645
- Novartis Investigative Site
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Krakow, Poland, 31 202
- Novartis Investigative Site
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Warszawa, Poland, 02-097
- Novartis Investigative Site
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Lodzkie
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Lodz, Lodzkie, Poland, 90 549
- Novartis Investigative Site
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Malopolskie
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Tarnow, Malopolskie, Poland, 33-100
- Novartis Investigative Site
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Maloposkie
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Krakow, Maloposkie, Poland, 31271
- Novartis Investigative Site
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Moscow, Russian Federation, 127644
- Novartis Investigative Site
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Saint Petersburg, Russian Federation, 197022
- Novartis Investigative Site
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Saint Petersburg, Russian Federation, 199106
- Novartis Investigative Site
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Saratov, Russian Federation, 410012
- Novartis Investigative Site
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St Petersburg, Russian Federation, 196601
- Novartis Investigative Site
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Madrid, Spain, 28041
- Novartis Investigative Site
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Madrid, Spain, 28034
- Novartis Investigative Site
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Madrid, Spain, 28040
- Novartis Investigative Site
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Valencia, Spain, 46026
- Novartis Investigative Site
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Zaragoza, Spain, 50009
- Novartis Investigative Site
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46010
- Novartis Investigative Site
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Madrid
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San Sebastian de los Reyes, Madrid, Spain, 28702
- Novartis Investigative Site
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Basel, Switzerland, 4031
- Novartis Investigative Site
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Tainan, Taiwan, 70403
- Novartis Investigative Site
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Taipei, Taiwan, 10002
- Novartis Investigative Site
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Taipei, Taiwan, 11217
- Novartis Investigative Site
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Sivas, Turkey, 58140
- Novartis Investigative Site
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Eskisehir
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Meselik, Eskisehir, Turkey, 26480
- Novartis Investigative Site
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Birmingham, United Kingdom, B16 8QQ
- Novartis Investigative Site
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Bournemouth, United Kingdom, BH7 7DW
- Novartis Investigative Site
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East Yorkshire, United Kingdom, HU16 5JQ
- Novartis Investigative Site
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Harrow, United Kingdom, HA1 3UJ
- Novartis Investigative Site
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Liverpool, United Kingdom, L9 7AL
- Novartis Investigative Site
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Newport, United Kingdom, NP20 2UB
- Novartis Investigative Site
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Stevenage, United Kingdom, SG1 4AB
- Novartis Investigative Site
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Somerset
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Axbridge, Somerset, United Kingdom, BS26 2BJ
- Novartis Investigative Site
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Wales
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Cardiff, Wales, United Kingdom, CF5 4AD
- Novartis Investigative Site
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Alabama
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Andalusia, Alabama, United States, 36420
- Novartis Investigative Site
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Arizona
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Glendale, Arizona, United States, 85306
- Novartis Investigative Site
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Mesa, Arizona, United States, 85206
- Novartis Investigative Site
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Phoenix, Arizona, United States, 85004
- Novartis Investigative Site
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Sun City West, Arizona, United States, 85375
- Novartis Investigative Site
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Tucson, Arizona, United States, 85723
- Novartis Investigative Site
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California
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Beverly Hills, California, United States, 90211
- Novartis Investigative Site
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Fresno, California, United States, 93720
- Novartis Investigative Site
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Loma Linda, California, United States, 92357
- Novartis Investigative Site
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Long Beach, California, United States, 90806
- Novartis Investigative Site
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Newport Beach, California, United States, 92663
- Novartis Investigative Site
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Santa Ana, California, United States, 92704
- Novartis Investigative Site
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Santa Ana, California, United States, 92705
- Novartis Investigative Site
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Torrance, California, United States, 90503
- Novartis Investigative Site
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Connecticut
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Danbury, Connecticut, United States, 06810
- Novartis Investigative Site
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Florida
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Clearwater, Florida, United States, 33756
- Novartis Investigative Site
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Edgewater, Florida, United States, 32132
- Novartis Investigative Site
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Hollywood, Florida, United States, 33312
- Novartis Investigative Site
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Homestead, Florida, United States, 33030
- Novartis Investigative Site
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Inverness, Florida, United States, 34452
- Novartis Investigative Site
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Jacksonville Beach, Florida, United States, 32050
- Novartis Investigative Site
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Miami, Florida, United States, 33133
- Novartis Investigative Site
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Miami, Florida, United States, 33144
- Novartis Investigative Site
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Miami, Florida, United States, 33176
- Novartis Investigative Site
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Naples, Florida, United States, 34102
- Novartis Investigative Site
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Port Orange, Florida, United States, 32127
- Novartis Investigative Site
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Tampa, Florida, United States, 33612
- Novartis Investigative Site
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Illinois
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Lombard, Illinois, United States, 60148
- Novartis Investigative Site
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Springfield, Illinois, United States, 62701
- Novartis Investigative Site
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Kansas
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Topeka, Kansas, United States, 66606
- Novartis Investigative Site
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Louisiana
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Eunice, Louisiana, United States, 70535
- Novartis Investigative Site
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Maryland
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Baltimore, Maryland, United States, 21229
- Novartis Investigative Site
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Michigan
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Saginaw, Michigan, United States, 48601
- Novartis Investigative Site
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Missouri
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Saint Louis, Missouri, United States, 63110
- Novartis Investigative Site
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Montana
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Kalispell, Montana, United States, 59901 3158
- Novartis Investigative Site
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Nevada
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Reno, Nevada, United States, 89502
- Novartis Investigative Site
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New Jersey
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Elmer, New Jersey, United States, 08318
- Novartis Investigative Site
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New York
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Buffalo, New York, United States, 14215
- Novartis Investigative Site
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North Carolina
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Gastonia, North Carolina, United States, 28054
- Novartis Investigative Site
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Ohio
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Cincinnati, Ohio, United States, 45219
- Novartis Investigative Site
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Oregon
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Oregon City, Oregon, United States, 97045
- Novartis Investigative Site
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Springfield, Oregon, United States, 97477
- Novartis Investigative Site
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South Carolina
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Fort Mill, South Carolina, United States, 29707
- Novartis Investigative Site
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Rock Hill, South Carolina, United States, 29732
- Novartis Investigative Site
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Summerville, South Carolina, United States, 29485
- Novartis Investigative Site
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Texas
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Dallas, Texas, United States, 75235
- Novartis Investigative Site
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Dallas, Texas, United States, 75226
- Novartis Investigative Site
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Gonzales, Texas, United States, 78629
- Novartis Investigative Site
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Houston, Texas, United States, 77030
- Novartis Investigative Site
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Lufkin, Texas, United States, 75904
- Novartis Investigative Site
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San Antonio, Texas, United States, 78229
- Novartis Investigative Site
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Washington
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Tacoma, Washington, United States, 98405
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key Inclusion Criteria:
- Chronic heart failure with current symptoms NYHA class II-IV
- Left ventricular ejection fraction > 40%
- NT-proBNP >= 125 pg/mL at screening visit
- Patient with evidence of adequate functioning to complete study assessments
Key Exclusion Criteria:
- Patients with acute decompensated heart failure requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs
- Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major CV surgery, or urgent percutaneous coronary intervention (PCI), carotid surgery or carotid angioplasty, history of stroke or transient ischemic attack within the 3 months prior to Screening visit or an elective PCI within 30 days prior to Screening visit
- Patients with history of hereditary or idiopathic angioedema or angioedema related to previous ACEi or ARB therapies
- Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor
Patients with one of the following:
- Patients with serum potassium >5.2 mmol/L (mEq/L) at Screening visit
- Patients with serum potassium >5.4 mmol/L (mEq/L) at any visit during run-in treatment period or at randomization visit
- Systolic blood pressure (SBP) ≥180 mmHg at Screening visit, or
- SBP <110 mmHg at Screening visit, or
- SBP <100 mmHg or symptomatic hypotension as determined by the investigator at Visit 103 or at randomization visit
- Body mass index (BMI) >45 kg/m^2
Patients with
- known pericardial constriction, genetic hypertrophic cardiomyopathy, infiltrative cardiomyopathy
- hemodynamically significant obstructive valvular disease
- Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 beats per minute
- Inability to perform cognitive battery or other study evaluations based on significant motor (e.g. hemiplegia, muscular-skeletal injury) or sensory (blindness, decreased or uncorrected visual or auditory acuity) skill
- Clinically significant cerebral pathology for example large cerebral aneurysm or space occupying lesion that may impact cognition as assessed by central MRI reader
- Mini mental state examination score less than 24 at screening
- Patients with a clinical diagnosis of Alzheimer's disease or other dementia syndromes or any indication for or current treatment with cholinesterase inhibitors and/or another prescription AD treatment (e.g. memantine).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LCZ696
Patients will receive LCZ696 at 100 mg twice daily during a single-blind treatment run-in period to ensure patients tolerate this medication before they are randomized.
Down-titration is not allowed during this period.
Patients who are able to tolerate LCZ696 100 mg twice daily are eligible to enter the randomized treatment period.
Patients randomized to receive LCZ696 will be given LCZ696 at 200 mg twice daily.
Patients will receive randomized study drug for three years.
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LCZ696 50, 100, and 200 mg tablets taken orally twice daily with matching placebo for valsartan
Placebo to match valsartan 40 mg, 80 mg, and 160 mg tablets
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Active Comparator: Valsartan
Patients will receive valsartan at 40mg and/or 80mg twice daily during a single-blind treatment run-in period.
Following the run-in period, patients randomized to receive valsartan will be given valsartan at 160 mg twice daily for three years.
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Valsartan 40, 80, and 160 mg tablets taken orally twice daily with matching placebo for LCZ696
Placebo to match LCZ696 50 mg, 100 mg, and 200 mg tablets
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change from baseline in the CogState Global Cognitive Composite Score (GCCS)
Time Frame: Baseline, week 156
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Change in cognition is assessed as a change in a Global Cognitive Composite Z score.
The cognitive composite comprises cognitive domains including attention, memory, and executive function.
A negative change from baseline will indicate worsening performance.
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Baseline, week 156
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change from baseline in cortical composite standardized uptake value ratio (SUVr)
Time Frame: Baseline, week 156
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Changes in amyloid plaque deposition over time will be assessed using florbetapir-18F.
The longitudinal change in the standardized uptake value ratio will be determined.
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Baseline, week 156
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Change from baseline in individual cognitive domains (memory, executive function, and attention)
Time Frame: Baseline, week 156
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Specific cognitive domains to be assessed include memory, executive function, and attention.
A negative change from baseline will indicate worsening performance.
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Baseline, week 156
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Change from baseline in the summary score of the instrumental activities of daily living (IADL)
Time Frame: Baseline, week 156
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Instrumental activities of daily living will be assessed using the functional activities questionnaire.
The functional activities questionnaire will be used as a standardized assessment of activities of daily living.
This questionnaire is typically used to distinguish normal subjects from subjects with mild to moderate cognitive impairment.
The test is made up of 10 questions that reflect a subject's ability to perform activities of daily living and to function independently.
Test scores range from 0 to 30, a score of 0 is completely normal where as a higher score denotes impairment.
Each of 10 questions is scored from 0, representing normal to 3, dependent on someone else to perform the activity.
A negative change from baseline denotes improvement.
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Baseline, week 156
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLCZ696B2320
- 2016-001254-17 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Clinical Trials on LCZ696
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Novartis PharmaceuticalsCompleted
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Novartis PharmaceuticalsCompletedHeart Failure and Reduced Ejection FractionUnited States
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Novartis PharmaceuticalsCompletedHypertensionUnited States, Spain, Philippines, Guatemala, Russian Federation, Argentina, Puerto Rico
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Novartis PharmaceuticalsCompletedChronic Heart Failure With Reduced Ejection FractionBelgium, Estonia, Denmark, Greece, United Kingdom, Germany, Latvia, Lithuania, Spain, Netherlands, Bulgaria, Finland, Poland, Czechia, Iceland, Sweden, France, Ireland, Norway
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University Hospital, MontpellierCompletedChronic Heart Failure | Sleep Apnea SyndromeFrance
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Novartis PharmaceuticalsCompletedEssential HypertensionChina, Korea, Republic of, Taiwan, Hong Kong, Thailand, Philippines, Singapore
-
Novartis PharmaceuticalsCompletedChronic Heart Failure With Reduced Ejection FractionGermany
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Novartis PharmaceuticalsCompletedHeart Failure | Erectile Dysfunction | Heart Failure, SystolicGermany
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Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI)Completed
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Novartis PharmaceuticalsCompletedHeart Failure With Reduced Ejection Fraction (HF-rEF)Japan