Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI

Acute Myocardial Infarction Clinical Trial

— PARADISE-MI  

Official title:

A Multi-center, Randomized, Double-blind, Active-controlled, Parallel-group Phase 3 Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Ramipril on Morbidity and Mortality in High Risk Patients Following an Acute Myocardial Infarction (AMI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02924727
• Other study ID #: CLCZ696G2301
• Secondary ID: 2016-002154-20
• Status: Completed
• Phase: Phase 3
• Start date: December 9, 2016
• Est. completion date: February 26, 2021

Study information

• Verified date: June 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of LCZ696 titrated to a target dose of 200 mg twice daily, compared to ramipril titrated to a target dose of 5 mg twice daily.

Description:

The purpose of this study is to evaluate the efficacy and safety of LCZ696 titrated to a target dose of 200 mg twice daily, compared to ramipril titrated to a target dose of 5 mg twice daily, in addition to conventional post-AMI treatment, in reducing the occurrence of composite endpoint of CV death, HF hospitalization and outpatient HF (time-to-first event analysis) in post-AMI patients with evidence of LV systolic dysfunction and/or pulmonary congestion, with no known prior history of chronic HF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5669
• Est. completion date: February 26, 2021
• Est. primary completion date: February 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients = 18 years of age.

2. Diagnosis of spontaneous AMI based on the universal MI definition* with randomization to occur between 12 hours and 7 days after index event presentation. (*patients with spontaneous MI event determined to be secondary to another medical condition such as anemia, hypotension, or arrhythmia OR thought to be caused by coronary vasospasm with document normal coronary arteries are not eligible; patients with clinical presentation thought to be related to Takotsubo cardiomyopathy are also not eligible)

3. Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous

treatment associated with the index MI event defined as:

• LVEF =40% after index MI presentation and prior to randomization and/or
• Pulmonary congestion requiring intravenous treatment with diuretics, vasodilators, vasopressors and/or inotropes, during the index hospitalization

4. At least one of the following 8 risk factors:

• Age = 70 years
• eGFR <60 mL/min/1.73 m^2 based on MDRD formula at screening visit
• Type I or II diabetes mellitus
• Documented history of prior MI
• Atrial fibrillation as noted by ECG, associated with index MI
• LVEF <30% associated with index MI
• Worst Killip class III or IV associated with index MI requiring intravenous treatment
• STEMI without reperfusion therapy within the first 24 hours after presentation

5. Hemodynamically stable defined as:

• SBP = 100 mmHg at randomization for patients who received ACEi/ARB during the last 24 hours prior to randomization
• SBP = 110 mmHg at randomization for patients who did not receive ACEi/ARB during the last 24 hours prior to randomization
• No IV treatment with diuretics, vasodilators, vasopressors and/or inotropes during the 24 hours prior to randomization

Key Exclusion Criteria:

1. Known history of chronic HF prior to randomization

2. Cardiogenic shock within the last 24 hours prior to randomization

3. Persistent clinical HF at the time of randomization

4. Coronary artery bypass graft (CABG) performed or planned for index MI

5. Clinically significant right ventricular MI as index MI

6. Symptomatic hypotension at screening or randomization

7. Patients with a known history of angioedema

8. Stroke or transient ischemic attack within one month prior to randomization

9. Known or suspected bilateral renal artery stenosis

10. Clinically significant obstructive cardiomyopathy

11. Open-heart surgery performed within one month prior to randomization or planned cardiac surgery w/in the 3 months prior to randomization

12. eGFR < 30 ml/min/1.73 m^2 as measured by MDRD at screening

13. Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at randomization

14. Known hepatic impairment (as evidenced by total bilirubin > 3.0 mg/dL or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as esophageal varices

15. Previous use of LCZ696

16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin) within the past 3 years with a life expectancy of less than 1year.

17. History of hypersensitivity to the study drugs or drugs of similar chemical classes or known intolerance or contraindications to study drugs or drugs of similar chemical classes including ACE inhibitors, ARB or NEP inhibitors

18. Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• LCZ696 (sacubitril/valsartan)
LCZ696 (sacubitril/valsartan) tablet will be available in 24/26 mg, 49/51 mg and 97/103 mg, respectively
• Ramipril
Ramipril 1.25 mg, 2.5 mg, and 5 mg oral capsules
• Placebo of LCZ696
Matching placebo of LCZ696 tablets
• Placebo of ramipril
Matching placebo of ramipril capsule
• Valsartan
Valsartan (VAL489) 40 mg and 80 mg tablets, two doses for 1 day to patients who were previously treated with ACE inhibitors receiving the last dose of that agent during the last 36 hours prior to randomization
• Placebo of valsartan
matching placebo of valsartan for one day to patients who will be randomized to received ramipril

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires	Caba
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad de Salta	Provincia De Salta
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Formosa
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Luis
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Tucuman	San Miguel De Tucuman
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Chemside	Queensland
Australia	Novartis Investigative Site	Geelong	Victoria
Australia	Novartis Investigative Site	Herston	Queensland
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Murdoch	Western Australia
Austria	Novartis Investigative Site	Braunau
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	St Poelten
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Brasschaat
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Turnhout
Belgium	Novartis Investigative Site	Yvoir
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Blumenau	SC
Brazil	Novartis Investigative Site	Campina Grande do Sul
Brazil	Novartis Investigative Site	Campinas	SP
Brazil	Novartis Investigative Site	Curitiba	Parana
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	Goiania	GO
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Jose
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Uberlandia	Minas Gerais
Bulgaria	Novartis Investigative Site	Blagoevgrad
Bulgaria	Novartis Investigative Site	Burgas
Bulgaria	Novartis Investigative Site	Burgas	BGR
Bulgaria	Novartis Investigative Site	Gabrovo
Bulgaria	Novartis Investigative Site	Kardzhali
Bulgaria	Novartis Investigative Site	Pernik
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia	BGR
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Sainte Foy	Quebec
Canada	Novartis Investigative Site	Terrebonne	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Canada	Novartis Investigative Site	Victoria	British Columbia
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Jinan	Shandong
China	Novartis Investigative Site	Jinshan	Shanghai
China	Novartis Investigative Site	Lanzhou	Gansu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shengyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Wenzhou	Zhejiang
China	Novartis Investigative Site	Wuhan
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xian	Shanxi
China	Novartis Investigative Site	Xicheng	Beijing
China	Novartis Investigative Site	Yanji	Jilin
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Cali	Valle Del Cauca
Colombia	Novartis Investigative Site	Medellin	Antioquia
Colombia	Novartis Investigative Site	Medellin	Antioquia
Croatia	Novartis Investigative Site	Cakovec
Croatia	Novartis Investigative Site	Zagreb
Croatia	Novartis Investigative Site	Zagreb	HRV
Czechia	Novartis Investigative Site	Brno Bohunice
Czechia	Novartis Investigative Site	Kladno	Czech Republic
Czechia	Novartis Investigative Site	Liberec	Czech Republic
Czechia	Novartis Investigative Site	Plzen-Bory
Czechia	Novartis Investigative Site	Prague 4
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Zlin	Czech Republic
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Glostrup
Denmark	Novartis Investigative Site	Herlev
Denmark	Novartis Investigative Site	Hvidovre
Denmark	Novartis Investigative Site	Svendborg
Denmark	Novartis Investigative Site	Vejle
Denmark	Novartis Investigative Site	Viborg
Finland	Novartis Investigative Site	Jyvaskyla
Finland	Novartis Investigative Site	Kaupio
Finland	Novartis Investigative Site	Tampere
France	Novartis Investigative Site	Bron
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Corbeil Essonnes
France	Novartis Investigative Site	Grenoble Cedex 9
France	Novartis Investigative Site	Marseille Cedex 8
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 18
France	Novartis Investigative Site	Pessac Cedex
France	Novartis Investigative Site	Toulouse Cedex
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Bad Krozingen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Coburg
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Esslingen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Guetersloh
Germany	Novartis Investigative Site	Hennigsdorf
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Koeln-Nippes
Germany	Novartis Investigative Site	Langen
Germany	Novartis Investigative Site	Leverkusen
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Moenchengladbach
Germany	Novartis Investigative Site	Neuss
Germany	Novartis Investigative Site	Neuwied
Germany	Novartis Investigative Site	Riesa
Germany	Novartis Investigative Site	Ruesselsheim
Germany	Novartis Investigative Site	Stadtlohn
Germany	Novartis Investigative Site	Vechta
Germany	Novartis Investigative Site	Villingen-Schwenningen
Germany	Novartis Investigative Site	Witten
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Alexandroupolis	Evros
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Larissa	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Pecs	Baranya
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szekesfehervar
Hungary	Novartis Investigative Site	Zalaegerszeg	Zala
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	DehraDun	Uttarakhand
India	Novartis Investigative Site	Gurgaon	Haryana
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Karamsad	Gujrat
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Madurai	Tamil NADU
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Secunderabad	Telangana
India	Novartis Investigative Site	Vadodara	Gujarat
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Lower Galilee
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Sefad
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Catanzaro	CZ
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Grosseto	GR
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Rimini	RN
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Sanremo	IM
Italy	Novartis Investigative Site	Trieste	TS
Korea, Republic of	Novartis Investigative Site	Cheongju si	Chungcheongbuk Do
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-do
Mexico	Novartis Investigative Site	Ciudad de Mexico
Mexico	Novartis Investigative Site	Culiacan Sinaloa	Distrito Federal
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Queretaro
Mexico	Novartis Investigative Site	San Luis Potosi
Mexico	Novartis Investigative Site	Torreon	Coahulia
Netherlands	Novartis Investigative Site	Alkmaar
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Amersfoort
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Beverwijk
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Ede
Netherlands	Novartis Investigative Site	Gouda
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Heemstede
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Leiderdorp
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sneek	The Netherlands
Netherlands	Novartis Investigative Site	Tilburg
Netherlands	Novartis Investigative Site	Uden
Netherlands	Novartis Investigative Site	Veldhoven
Netherlands	Novartis Investigative Site	Venlo
Netherlands	Novartis Investigative Site	Zutphen
Netherlands	Novartis Investigative Site	Zwolle
Norway	Novartis Investigative Site	Gralum
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Stavanger
Peru	Novartis Investigative Site	Bellavista	Lima
Peru	Novartis Investigative Site	Cercado De Lima	Lima
Peru	Novartis Investigative Site	Jesus Maria	Lima
Peru	Novartis Investigative Site	Lima
Philippines	Novartis Investigative Site	Iloilo city	Iloilo
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Quezon City	Manila
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Lubin
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Portugal	Novartis Investigative Site	Almada
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Carnaxide	Lisboa
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Covilha
Portugal	Novartis Investigative Site	Faro
Portugal	Novartis Investigative Site	Guimaraes
Portugal	Novartis Investigative Site	Leiria
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Vila Real
Romania	Novartis Investigative Site	Baia Mare
Romania	Novartis Investigative Site	Braila	ROM
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Bucuresti	District 4
Romania	Novartis Investigative Site	Cluj Napoca	Jud Cluj
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Iasi	Jud Iasi
Romania	Novartis Investigative Site	Oradea	Jud Bihor
Romania	Novartis Investigative Site	Pitesti	Arges
Romania	Novartis Investigative Site	Sibiu
Romania	Novartis Investigative Site	Suceava	ROM
Romania	Novartis Investigative Site	Targu Mures	Mures
Romania	Novartis Investigative Site	Timisoara	Timis
Romania	Novartis Investigative Site	Timisoara
Romania	Novartis Investigative Site	Timisoara
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Krasnodar
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Murmansk
Russian Federation	Novartis Investigative Site	N.Novgorod
Russian Federation	Novartis Investigative Site	Nizhnii Novgorod
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	S.-Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Sochy
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Tomsk
Russian Federation	Novartis Investigative Site	Yekaterinburg
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Banska Bystrica	SVK
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Nitra	Slovak Republic
Slovakia	Novartis Investigative Site	Presov
South Africa	Novartis Investigative Site	Cape Town	Western Cape
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	George	Western Cape
South Africa	Novartis Investigative Site	Pinelands	Cape Town
South Africa	Novartis Investigative Site	Worcester
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Leon	Castilla Y Leon
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Villamartin	Cadiz
Sweden	Novartis Investigative Site	Goethenburg
Sweden	Novartis Investigative Site	Helsingborg
Sweden	Novartis Investigative Site	Helsingborg
Sweden	Novartis Investigative Site	Malmo
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Stockholm	SE
Sweden	Novartis Investigative Site	Uppsala
Sweden	Novartis Investigative Site	Vasteras
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Luzern 16
Switzerland	Novartis Investigative Site	St Gallen
Taiwan	Novartis Investigative Site	New Taipei
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Taiwan	Novartis Investigative Site	Yilan
Thailand	Novartis Investigative Site	Bangkok	THA
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Turkey	Novartis Investigative Site	Ankara-Cankaya
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Kucukcekmece Istanbul
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Meselik	Eskisehir
Turkey	Novartis Investigative Site	Sivas
Turkey	Novartis Investigative Site	Trabzon
United Kingdom	Novartis Investigative Site	Basingstoke	Hampshire
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bournemouth
United Kingdom	Novartis Investigative Site	Clydebank	West Dumbartonshire
United Kingdom	Novartis Investigative Site	Craigavon	Northern Ireland
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	Lincoln	Lincolnshire
United Kingdom	Novartis Investigative Site	Middlesbrough
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Worcester
United States	Novartis Investigative Site	Alexandria	Louisiana
United States	Novartis Investigative Site	Bakersfield	California
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Bellevue	Washington
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Brandon	Florida
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Carmichael	California
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Coeur d'Alene	Idaho
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Covington	Louisiana
United States	Novartis Investigative Site	Cumming	Georgia
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Danville	Virginia
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Duluth	Minnesota
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Erie	Pennsylvania
United States	Novartis Investigative Site	Falls Church	Virginia
United States	Novartis Investigative Site	Flushing	New York
United States	Novartis Investigative Site	Gilbert	Arizona
United States	Novartis Investigative Site	Grand Forks	North Dakota
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Hackensack	New Jersey
United States	Novartis Investigative Site	Hammond	Louisiana
United States	Novartis Investigative Site	Hattiesburg	Mississippi
United States	Novartis Investigative Site	Hershey	Pennsylvania
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Huntsville	Alabama
United States	Novartis Investigative Site	Iowa City	Iowa
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Jacksonville Beach	Florida
United States	Novartis Investigative Site	Johns Creek	Georgia
United States	Novartis Investigative Site	Kalamazoo	Michigan
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Lansing	Michigan
United States	Novartis Investigative Site	Lebanon	New Hampshire
United States	Novartis Investigative Site	Lee's Summit	Missouri
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Los Alamitos	California
United States	Novartis Investigative Site	Lynchburg	Virginia
United States	Novartis Investigative Site	Manassas	Virginia
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Muncie	Indiana
United States	Novartis Investigative Site	Munster	Indiana
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	North Kansas City	Missouri
United States	Novartis Investigative Site	Northridge	California
United States	Novartis Investigative Site	Ocala	Florida
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orange	California
United States	Novartis Investigative Site	Petoskey	Michigan
United States	Novartis Investigative Site	Rapid City	South Dakota
United States	Novartis Investigative Site	Richmond	Indiana
United States	Novartis Investigative Site	Robbinsdale	Minnesota
United States	Novartis Investigative Site	Rockville	Maryland
United States	Novartis Investigative Site	Saginaw	Michigan
United States	Novartis Investigative Site	Saint Cloud	Minnesota
United States	Novartis Investigative Site	Saint Paul	Minnesota
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Slidell	Louisiana
United States	Novartis Investigative Site	Southfield	Michigan
United States	Novartis Investigative Site	Springfield	Missouri
United States	Novartis Investigative Site	Sylmar	California
United States	Novartis Investigative Site	Thomasville	Georgia
United States	Novartis Investigative Site	Valhalla	New York
United States	Novartis Investigative Site	Webster	Texas
United States	Novartis Investigative Site	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Croatia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With First CEC (Clinical Endpoint Committee) Confirmed Primary Composite Endpoint	A confirmed composite endpoint includes cardiovascular (CV) death, heart failure (HF) hospitalization, or outpatient heart failure	From randomization to first occurrence (up to approximately 43 months)
Secondary	Number of Participants With a Confirmed Composite of CV Death or HF Hospitalization	A confirmed composite endpoint for this outcome measure includes cardiovascular death or heart failure hospitalization.	Time from randomization to first occurrence (up to approximately 43 months)
Secondary	Number of Participants With a Confirmed Composite of HF Hospitalization or Outpatient HF	A confirmed composite endpoint includes first occurrence of heart failure hospitalization or outpatient heart failure	Time from randomization to first occurrence (approximately up to 43 months)
Secondary	Number of Participants With a Confirmed Composite of CV Death, Non-fatal Spontaneous Myocardial Infarction or Non-fatal Stroke	A confirmed composite endpoint for this outcome measure includes cardiovascular death, non-fatal spontaneous myocardial infarction or non-fatal stroke	Time from randomization to first occurrence (approximately up to 43 months)
Secondary	Total Number of Confirmed Composite Endpoints	A confirmed composite endpoint includes cardiovascular death, heart failure hospitalization, non-fatal spontaneous MI hospitalization, and non-fatal stroke hospitalization	Time from randomization to end of study (approximately up to 43 months)
Secondary	All-cause Mortality for Full Analysis Set (FAS)	All-cause mortality defined as deaths related to Cardiovascular (CV) and non-CV events for patients in the Full Analysis Set up to a cut-off date of 31-Dec-2020.	Time from randomization to death (approximately up to 43 months)