Clinical trial NCT02661217: Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event
Official title: A Multicenter, Randomized, Open Label, Parallel Group Study Comparing Pre-discharge and posT-discharge tReatment Initiation With LCZ696 in heArt Failure patieNtS With Reduced ejectIon-fracTion hospItalized for an Acute decOmpensation eveNt (ADHF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Acute decompensated heart failure
Reduced ejection fraction
Pre-discharge treatment
Post-discharge treatment
Angiotensin receptor neprilysine inhibitor
HFrEF
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-01-22
Enrollment: 1002
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.


Eligibility criteria: Inclusion Criteria:

1. Patients hospitalized due to acute decompensated HF episode (ADHF) as primary diagnosis) and consistent Signs \& Symptoms
2. Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction: Left ventricular ejection fraction ≤ 40% at Screening
3. Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to Randomization
4. Stabilized (while in the hospital) for at least 24 hours leading to Randomization.
5. Meeting one of the following criteria:

   * Patients on any dose of ACEI or ARB at screening
   * ACEI/ARB naïve patients and patients not on ACEI or ARB for at least 4 weeks before screening.

Exclusion Criteria:

1. History of hypersensitivity to the sacubitril, valsartan, or any ARBs, NEP inhibitors or to any of the LCZ696 excipients.
2. Symptomatic hypotension and/or a SBP below 110 mm Hg or SBP above 180 mm Hg prior to randomization
3. End stage renal disease at Screening; or estimated GFR below 30 mL/min/1.73 m2 (as measured by MDRD formula at Randomization.
4. Serum potassium above 5.4 mmol/L at Randomization.
5. Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy
6. Severe hepatic impairment, biliary cirrhosis and cholestasis

Primary outcomes:
measure: Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization
timeFrame: 10 weeks after Randomization
Secondary outcomes:
measure: Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid
timeFrame: 10 weeks after Randomization
measure: Percentage of Patients Achieving and Maintaining Any Dose of LCZ696
timeFrame: 10 weeks after Randomization
measure: Percentage of Patients Permanently Discontinued From Treatment
timeFrame: 10 weeks after Randomization AND 26 weeks after randomization
Other outcomes:
Locations:
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Villa Maria
country: Argentina
facility: Novartis Investigative Site
state: Cordoba
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Salta
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Huy
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Ronse
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Karlovy Vary
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Liberec
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Tabor
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Trebic
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Beroun
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
city: JIhlava
country: Czechia
facility: Novartis Investigative Site
city: Kolin
country: Czechia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Slany
country: Czechia
facility: Novartis Investigative Site
city: Amiens
country: France
facility: Novartis Investigative Site
city: Besancon cedex
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex
country: France
facility: Novartis Investigative Site
city: Tourcoing
country: France
facility: Novartis Investigative Site
city: Valenciennes
country: France
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Leverkusen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dortmund
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Koeln-Nippes
country: Germany
facility: Novartis Investigative Site
city: Langen
country: Germany
facility: Novartis Investigative Site
city: Lübeck
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Moenchengladbach
country: Germany
facility: Novartis Investigative Site
city: Neuwied
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Ruesselsheim
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Cremona
country: Italy
facility: Novartis Investigative Site
state: CR
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Milano
country: Italy
facility: Novartis Investigative Site
city: El Chouf
country: Lebanon
facility: Novartis Investigative Site
state: LBN
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Alesund
country: Norway
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Gralum
country: Norway
facility: Novartis Investigative Site
city: Lillehammer
country: Norway
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
state: Lodzkie
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Pulawy
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Vila Real
country: Portugal
facility: Novartis Investigative Site
state: Portuigal
city: Amadora
country: Portugal
facility: Novartis Investigative Site
city: Aveiro
country: Portugal
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Covilha
country: Portugal
facility: Novartis Investigative Site
city: Guimaraes
country: Portugal
facility: Novartis Investigative Site
city: Leiria
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Gatchina
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Dammam
country: Saudi Arabia
facility: Novartis Investigative Site
city: Jeddah
country: Saudi Arabia
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Dunajska Streda
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Liptovsky Mikulas
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Dolny Kubin
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Presov
country: Slovakia
facility: Novartis Investigative Site
city: Rimavska Sobota
country: Slovakia
facility: Novartis Investigative Site
city: Trnava
country: Slovakia
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sanlucar de Barrameda
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Barcelona/ Cataluny/Espanya
city: Villamartin
country: Spain
facility: Novartis Investigative Site
state: Cadiz
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Olot
country: Spain
facility: Novartis Investigative Site
state: Girona
city: Mostoles
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Joenkoeping
country: Sweden
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
city: Eskisehir
country: Turkey
facility: Novartis Investigative Site
state: Meselik
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Sivas
country: Turkey
facility: Novartis Investigative Site
city: Westcliff on Sea
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
city: Basingstoke
country: United Kingdom
facility: Novartis Investigative Site
state: Hampshire
city: Ashford
country: United Kingdom
facility: Novartis Investigative Site
state: Kent
city: Bridgend
country: United Kingdom
facility: Novartis Investigative Site
state: Mid Glamorgan
city: Portadown
country: United Kingdom
facility: Novartis Investigative Site
state: Nothern Ireland
city: Sunderland
country: United Kingdom
facility: Novartis Investigative Site
state: Tyne And Wear
city: Blackpool
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Middlesbrough
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Norwich
country: United Kingdom
facility: Novartis Investigative Site
city: Swindon
country: United Kingdom
facility: Novartis Investigative Site
city: York
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Pascual-Figal D, Wachter R, Senni M, Bao W, Noe A, Schwende H, Butylin D, Prescott MF; TRANSITION Investigators. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study. JACC Heart Fail. 2020 Oct;8(10):822-833. doi: 10.1016/j.jchf.2020.05.012. Epub 2020 Aug 12.
citation: Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail. 2020 Feb;22(2):303-312. doi: 10.1002/ejhf.1670. Epub 2019 Dec 9.
citation: Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bohmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noe A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.
citation: Pascual-Figal D, Wachter R, Senni M, Belohlavek J, Noe A, Carr D, Butylin D. Rationale and design of TRANSITION: a randomized trial of pre-discharge vs. post-discharge initiation of sacubitril/valsartan. ESC Heart Fail. 2018 Apr;5(2):327-336. doi: 10.1002/ehf2.12246. Epub 2017 Dec 14.