A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients

Heart Failure With Preserved Ejection Fraction Clinical Trial

— PARALLAX  

Official title:

A 24-week, Randomized, Double-blind, Multi-center, Parallel LCZ696 on NT-proBNP, Exercise Capacity, Symptoms and Safety Compared to Individualized Medical Management of Comorbidities in Patients With Heart Failure and Preserved Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03066804
• Other study ID #: CLCZ696D2302
• Secondary ID: 2016-003410-28
• Status: Completed
• Phase: Phase 3
• Start date: August 22, 2017
• Est. completion date: October 28, 2019

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the superiority of LCZ696 over individualized medical therapy for comorbidities in reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) and improving exercise capacity and HF symptoms in patients with heart failure with preserved ejection fraction (HFpEF).

Description:

This study was a 24-week, randomized, double-blind, multi-center, parallel group, active controlled study to evaluate sacubitril/valsartan compared to individualized medical therapy on NT proBNP, exercise capacity, symptoms and QoL in patients with heart failure and preserved left ventricular ejection (HFpEF) fraction (LVEF > 40%). Patients were initially stratified into one of three strata according to prior treatment for comorbidities: Angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or no prior renin angiotensin system inhibitors (RASi). Patients in each stratum were randomized in a 1:1 ratio and received either sacubitril/valsartan or comparator (i.e.

enalapril for patients in ACEi strata, valsartan for patients in the ARB strata and placebo for patients in the No RASi strata). There was no designated proportion of patients planned in each stratum; the strata were populated based upon the patient's prior treatment regimen. The study consisted of a screening epoch of up to 2 weeks and a randomized treatment epoch of 24 weeks, which included a 1 to 4 week study drug up-titration epoch followed by a 20 to 23 week maintenance epoch. Uptitration to target doses was recommended to occur within the first four weeks of the study, and was performed by Investigator's discretion based on the patient's clinical status.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2572
• Est. completion date: October 28, 2019
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Left ventricular ejection fraction (LVEF) >40% by echo within 6 months prior to study entry or during the screening epoch

• Symptom(s) of heart failure (HF) requiring treatment with diuretics (including loop, or thiazide diuretics, or mineralocorticoid antagonist [MRAs]) for at least 30 days prior to study entry

• NYHA class II-IV

• Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram.

• NT-proBNP > 220 pg/mL for patients with no atrial fibrillation/atrial flutter (AF) or >600 pg/mL for patients with AF

• KCCQ clinical summary score < 75

• Patients on ACEi or ARB therapy must have a history of HTN

Exclusion Criteria:

• Any prior measurement of LVEF = 40%, under stable conditions

• Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention (PCI) within 3 months or an elective PCI within 30 days prior to study entry

• Any clinical event within the 6 months prior to Visit 1 that could have reduced the LVEF (eg MI, coronary artery bypass graft [CABG]), unless an echo measurement was performed after the event confirming the LVEF to be >40%

• Current (within 30 days from Visit 1) acute decompensated HF requiring therapy.

• Current (within 30 days from Visit 1) use of renin inhibitor(s), dual RAS blockade or LCZ696

• History of hypersensitivity to LCZ696 or its components

• Patients with a known history of angioedema

• Walk distance primarily limited by non-cardiac comorbid conditions at study entry

• Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dL males and < 9.5 g/dL females, or body mass index (BMI) > 40 kg/m^2.

• Systolic blood pressure (SBP) = 180 mmHg at study entry, or SBP >150 mmHg and <180 mmHg at study entry unless the patient is receiving 3 or more antihypertensive drugs, or SBP < 110 mmHg at study entry.

• Patients with HbA1c > 7.5% not treated for diabetes

• Patients with prior major organ transplant or intent to transplant (ie on transplant list)

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

• Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at study entry

• History or presence of any other disease with a life expectancy of < 3 years

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

Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• sacubitril/valsartan
Sacubitril/valsartan is available as 24 mg/26 mg, 49 mg/51 mg, 97 mg/103 mg, respectively in tablet form to be taken orally
• Enalapril
Enalapril is available as 2.5 mg, 5 mg, and 10 mg tablet form to be taken orally
• Valsartan
Valsartan is available as 40 mg, 80 mg, 160 mg tablet form to be taken orally
• Placebo to match sacubitril/valsartan
Placebo to match LCZ696 50 mg, 100 mg, 200 mg tablet form to be taken orally
• Placebo to match enalapril
Placebo to match enalapril 2.5 mg, 5 mg, 10 mg tablet form to be taken orally
• Placebo to match valsartan
Placebo to match valsartan 40 mg, 80 mg, 160 mg tablet form to be taken orally

Locations

Country	Name	City	State
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	Cordoba
Argentina	Novartis Investigative Site	Formosa
Argentina	Novartis Investigative Site	Posadas	Misiones
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
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	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Tucuman	San Miguel De Tucuman
Austria	Novartis Investigative Site	Braunau
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Hall in Tirol
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Salzburg
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Heusden-Zolder
Belgium	Novartis Investigative Site	Huy
Belgium	Novartis Investigative Site	Kortrijk
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Blumenau	SC
Brazil	Novartis Investigative Site	Campinas	SP
Brazil	Novartis Investigative Site	Canoas	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Curitiba	Parana
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	Goiania	GO
Brazil	Novartis Investigative Site	Goiania	GO
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Ribeirao Preto	SP
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Bulgaria	Novartis Investigative Site	Burgas
Bulgaria	Novartis Investigative Site	Pazardzhik
Bulgaria	Novartis Investigative Site	Pernik
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Shumen
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Veliko Tarnovo
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Oakville	Ontario
Canada	Novartis Investigative Site	St-Georges Beauce	Quebec
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Cali	Valle Del Cauca
Colombia	Novartis Investigative Site	Medellin	Antioquia
Colombia	Novartis Investigative Site	Monteria
Colombia	Novartis Investigative Site	San Gil
Czechia	Novartis Investigative Site	Brandys nad Labem	Czech Republic
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Cesky Krumlov	Czech Republic
Czechia	Novartis Investigative Site	Jablonec nad Nisou	Czech Republic
Czechia	Novartis Investigative Site	JIhlava	CZE
Czechia	Novartis Investigative Site	Kolin
Czechia	Novartis Investigative Site	Kromeriz	Czech Republic
Czechia	Novartis Investigative Site	Liberec	Czech Republic
Czechia	Novartis Investigative Site	Louny	Czech Republic
Czechia	Novartis Investigative Site	Olomouc Lazce
Czechia	Novartis Investigative Site	Pardubice	Czech Republic
Czechia	Novartis Investigative Site	Plzen	Czech Republic
Czechia	Novartis Investigative Site	Policska	CZE
Czechia	Novartis Investigative Site	Prerov
Czechia	Novartis Investigative Site	Svitavy	Czech Republic
Czechia	Novartis Investigative Site	Tabor	Czech Republic
Czechia	Novartis Investigative Site	Trebic	Czech Republic
Czechia	Novartis Investigative Site	Valasske Mezirici
Denmark	Novartis Investigative Site	Copenhagen NV
Denmark	Novartis Investigative Site	Hvidovre
Denmark	Novartis Investigative Site	Randers
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Besancon cedex
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Corbeil Essonnes
France	Novartis Investigative Site	Le Coudray
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Limoges cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Rennes Cedex 9
France	Novartis Investigative Site	Tourcoing
France	Novartis Investigative Site	Valenciennes
Germany	Novartis Investigative Site	Bad Homburg
Germany	Novartis Investigative Site	Bad Oeynhausen
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin Buch
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum Wattenscheid
Germany	Novartis Investigative Site	Brueel
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Coburg
Germany	Novartis Investigative Site	Detmold	NRW
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden	Sachsen
Germany	Novartis Investigative Site	Elsterwerda
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen	DEU
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Fuerth
Germany	Novartis Investigative Site	Fulda
Germany	Novartis Investigative Site	Halle Saale
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hassloch
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln-Nippes
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Lüneburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Muehldorf
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Munich
Germany	Novartis Investigative Site	Neuruppin
Germany	Novartis Investigative Site	Nienburg
Germany	Novartis Investigative Site	Nuremberg
Germany	Novartis Investigative Site	Papenburg
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Riesa
Germany	Novartis Investigative Site	Rodgau
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Rotenburg an der Fulda
Germany	Novartis Investigative Site	Ruesselsheim
Germany	Novartis Investigative Site	Schwaebisch Hall
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Stadtlohn
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wallerfing
Germany	Novartis Investigative Site	Wedel
Germany	Novartis Investigative Site	Wismar
Germany	Novartis Investigative Site	Wuerzburg
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest	HUN
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Mosanmagyarovar
Hungary	Novartis Investigative Site	Szeged
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	India
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Manipal	Karnataka
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Nashik	Maharastra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Vadodara	Gujarat
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Be'er Sheva
Israel	Novartis Investigative Site	Hadera
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Cona
Italy	Novartis Investigative Site	Cortona	AR
Italy	Novartis Investigative Site	Legnano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Rovigo	RO
Italy	Novartis Investigative Site	San Vito al Tagliamento
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Sesto San Giovanni	MI
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Liepaja	LVA
Latvia	Novartis Investigative Site	Ogre
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Queretaro
Mexico	Novartis Investigative Site	San Luis Potosi
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Deventer
Netherlands	Novartis Investigative Site	Doetinchem
Netherlands	Novartis Investigative Site	Gouda
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Hardenberg
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Stadskanaal
Netherlands	Novartis Investigative Site	Tilburg
Netherlands	Novartis Investigative Site	Venlo
Peru	Novartis Investigative Site	Callao
Peru	Novartis Investigative Site	Cercado De Lima	Lima
Peru	Novartis Investigative Site	Jesus Maria	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Peru	Novartis Investigative Site	San Miguel	Lima
Peru	Novartis Investigative Site	Trujillo	La Libertad
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Penafiel
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Viana do Castelo
Portugal	Novartis Investigative Site	Vila Real
Romania	Novartis Investigative Site	Bacau
Romania	Novartis Investigative Site	Baia Mare
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	Craiova
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Pitesti
Romania	Novartis Investigative Site	Targu Mures
Romania	Novartis Investigative Site	Targu Mures
Romania	Novartis Investigative Site	Timisoara
Romania	Novartis Investigative Site	Timisoara	Timis
Romania	Novartis Investigative Site	Timisoara	Timis
Romania	Novartis Investigative Site	Tirgoviste
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Gatchina
Russian Federation	Novartis Investigative Site	Ivanovo
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	Nizhnii Novgorod
Russian Federation	Novartis Investigative Site	Perm
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Rostov on Don
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	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Tyumen
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yekaterinburg
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Kragujevac
Serbia	Novartis Investigative Site	Nis
Serbia	Novartis Investigative Site	Niska Banja
Serbia	Novartis Investigative Site	Sremska Kamenica
Slovakia	Novartis Investigative Site	Bardejov
Slovakia	Novartis Investigative Site	Bardejov
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava	SVK
Slovakia	Novartis Investigative Site	Dolny Kubin
Slovakia	Novartis Investigative Site	Handlova	SVK
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Lucenec
Slovakia	Novartis Investigative Site	Moldava nad Bodvou
Slovakia	Novartis Investigative Site	Namestovo	Slovak Republic
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Povazska Bystrica
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Presov	Slovak Republic
Slovakia	Novartis Investigative Site	Snina
Slovakia	Novartis Investigative Site	Svidnik
Slovakia	Novartis Investigative Site	Trnava
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Huelva	Andalucia
Spain	Novartis Investigative Site	Las Palmas De Gran Canarias
Spain	Novartis Investigative Site	Lerida	Cataluna
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Manises	Valencia
Spain	Novartis Investigative Site	Puerto Real	Cadiz
Spain	Novartis Investigative Site	San Sebastian de los Reyes	Madrid
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Torrevieja (Alicante)	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Villamartin	Cadiz
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Muang
Thailand	Novartis Investigative Site	Ubon Ratchathani
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Bursa
Turkey	Novartis Investigative Site	Eskisehir	Meselik
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	Mersin
Turkey	Novartis Investigative Site	Sivas
Turkey	Novartis Investigative Site	Talas / Kayseri
United Kingdom	Novartis Investigative Site	Addlestone	Surrey
United Kingdom	Novartis Investigative Site	Chesterfield	Derbyshire
United Kingdom	Novartis Investigative Site	Craigavon	Northern Ireland
United Kingdom	Novartis Investigative Site	High Wycombe	Buckinghamshire
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Stockton on Tees	Cleveland
United Kingdom	Novartis Investigative Site	Sunderland	Tyne And Wear
United Kingdom	Novartis Investigative Site	Wansford	Peterborough
United Kingdom	Novartis Investigative Site	York
United States	Novartis Investigative Site	Abington	Pennsylvania
United States	Novartis Investigative Site	Alexandria	Louisiana
United States	Novartis Investigative Site	Andalusia	Alabama
United States	Novartis Investigative Site	Arlington Heights	Illinois
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Bradenton	Florida
United States	Novartis Investigative Site	Chalmette	Louisiana
United States	Novartis Investigative Site	Corvallis	Oregon
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Falls Church	Virginia
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Houma	Louisiana
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Long Beach	California
United States	Novartis Investigative Site	Lufkin	Texas
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Santa Ana	California
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sioux Falls	South Dakota
United States	Novartis Investigative Site	Stamford	Connecticut
United States	Novartis Investigative Site	Sylmar	California
United States	Novartis Investigative Site	Thomasville	Georgia
United States	Novartis Investigative Site	Tomball	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Guatemala,  Hungary,  India,  Israel,  Italy,  Latvia,  Lithuania,  Mexico,  Netherlands,  Peru,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Week 12	To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in reducing NT-proBNP from baseline at Week 12 in patients with HFpEF	Baseline, week 12
Primary	Change From Baseline in 6 Minute Walk Distance (6MWD) at Week 24	Change from baseline in 6-minute walk distance (6MWD) will be reported at Week 24. The 6 MWT will be performed in accordance with the guidelines of the American Thoracic Society 2002.	Baseline, week 24
Secondary	Mean Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at Week 24	The KCCQ is a self-administered questionnaire that requires 4 to 6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). The CSS is a combined score based upon the clinical symptoms and physical function domains of the questionnaire. Scores are transformed to a range of 0 - 100, in which higher scores reflect better health status.	Baseline, Week 24
Secondary	Percentage of Patients With = 5-points Deterioration in KCCQ Clinical Symptom Score(CSS) at Week 24	Percentage of patients with KCCQ CSS deterioration = 5-points will be reported at Week 24. The KCCQ is a self-administered questionnaire that requires 4 to 6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). The CSS is a combined score based upon the clinical symptoms and physical function domains of the questionnaire. Scores are transformed to a range of 0 - 100, in which higher scores reflect better health status.	Baseline, Week 24
Secondary	Percentage of Patients With = 5-points Improvement in KCCQ Clinical Symptom Score(CSS) at Week 24	Percentage of patients with KCCQ CSS improvement = 5-points will be reported at Week 24. The KCCQ is a self-administered questionnaire that requires 4 to 6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). The CSS is a combined score based upon the clinical symptoms and physical function domains of the questionnaire. Scores are transformed to a range of 0 - 100, in which higher scores reflect better health status.	Baseline, Week 24
Secondary	Change From Baseline in NYHA Functional Class at Week 24	NYHA classification is a subjective physician's assessment of patient's functional capacity and symptomatic status and can change frequently over time.; Class I - No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF Class II - Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF Class III - Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF Class IV - Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest; The NYHA class change will be analyzed as a three category ordinal variable with levels: "improved", "unchanged", and "worsened", defined by at least one class improvement, no change, at least one class worsening, in NYHA class, respectively.	Baseline, week 24
Secondary	Change From Baseline in The Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24	The SF-36 PCS score reflects the measure of quality of life based on the 36 questions which evaluate the person's physical, emotional, and mental status, including general health. Specifically, the SF-36 PCS score focuses on assessing the person's physical status. The score ranges from 0 to 100 with a higher score indicating a better status of physical wellbeing (range = 0 "worst"-100 "best").	Baseline, Week 24

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com