Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event

Heart Failure With Reduced Ejection Fraction Clinical Trial

— TRANSITION  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02661217
• Other study ID #: CLCZ696B2401
• Secondary ID: 2015-003266-87
• Status: Completed
• Phase: Phase 4
• Start date: February 12, 2016
• Est. completion date: June 20, 2018

Study information

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

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1002
• Est. completion date: June 20, 2018
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• LCZ696
LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food. The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	Salta
Argentina	Novartis Investigative Site	Tucuman
Argentina	Novartis Investigative Site	Villa Maria	Cordoba
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Huy
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Ronse
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Czechia	Novartis Investigative Site	Beroun	CZE
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Brno Bohunice
Czechia	Novartis Investigative Site	JIhlava
Czechia	Novartis Investigative Site	Karlovy Vary	Czech Republic
Czechia	Novartis Investigative Site	Kolin
Czechia	Novartis Investigative Site	Liberec	Czech Republic
Czechia	Novartis Investigative Site	Olomouc
Czechia	Novartis Investigative Site	Ostrava	CZE
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Slany
Czechia	Novartis Investigative Site	Tabor	Czech Republic
Czechia	Novartis Investigative Site	Trebic	Czech Republic
France	Novartis Investigative Site	Amiens
France	Novartis Investigative Site	Besancon cedex
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Toulouse Cedex
France	Novartis Investigative Site	Tourcoing
France	Novartis Investigative Site	Valenciennes
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Koeln-Nippes
Germany	Novartis Investigative Site	Langen
Germany	Novartis Investigative Site	Leverkusen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Lübeck
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Moenchengladbach
Germany	Novartis Investigative Site	Neuwied
Germany	Novartis Investigative Site	Oldenburg
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Ruesselsheim
Germany	Novartis Investigative Site	Witten
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Cremona	CR
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Roma	RM
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	El Chouf	LBN
Lebanon	Novartis Investigative Site	Saida
Norway	Novartis Investigative Site	Alesund
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Gralum
Norway	Novartis Investigative Site	Lillehammer
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz	Lodzkie
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Pulawy
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Amadora
Portugal	Novartis Investigative Site	Aveiro
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Covilha
Portugal	Novartis Investigative Site	Guimaraes
Portugal	Novartis Investigative Site	Leiria
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Vila Real	Portuigal
Russian Federation	Novartis Investigative Site	Gatchina
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Saudi Arabia	Novartis Investigative Site	Dammam
Saudi Arabia	Novartis Investigative Site	Jeddah
Saudi Arabia	Novartis Investigative Site	Riyadh
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Dolny Kubin
Slovakia	Novartis Investigative Site	Dunajska Streda	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Liptovsky Mikulas	Slovak Republic
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Rimavska Sobota
Slovakia	Novartis Investigative Site	Trnava
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Barcelona	Barcelona/ Cataluny/Espanya
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Mostoles	Madrid
Spain	Novartis Investigative Site	Olot	Girona
Spain	Novartis Investigative Site	Sanlucar de Barrameda	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Villamartin	Cadiz
Sweden	Novartis Investigative Site	Goteborg
Sweden	Novartis Investigative Site	Joenkoeping
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Geneve 14
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Eskisehir	Meselik
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Sivas
United Kingdom	Novartis Investigative Site	Ashford	Kent
United Kingdom	Novartis Investigative Site	Basingstoke	Hampshire
United Kingdom	Novartis Investigative Site	Blackpool
United Kingdom	Novartis Investigative Site	Bridgend	Mid Glamorgan
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
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	Portadown	Nothern Ireland
United Kingdom	Novartis Investigative Site	Sunderland	Tyne And Wear
United Kingdom	Novartis Investigative Site	Swindon
United Kingdom	Novartis Investigative Site	Westcliff on Sea	Essex
United Kingdom	Novartis Investigative Site	York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Belgium,  Canada,  Czechia,  France,  Germany,  Italy,  Lebanon,  Norway,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization	Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10	10 weeks after Randomization
Secondary	Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid	Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10	10 weeks after Randomization
Secondary	Percentage of Patients Achieving and Maintaining Any Dose of LCZ696	Percentage of patients achieving any dose of LCZ696 for at least 2 weeks leading to 10 weeks of treatment	10 weeks after Randomization
Secondary	Percentage of Patients Permanently Discontinued From Treatment	Percentage of patients permanently discontinued from LCZ696 (1) up to week 10 due to AEs, and (2) up to week 26 due to any reasons	10 weeks after Randomization AND 26 weeks after randomization

External Links

•   Wacther R. et al.: Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.