Clinical trial NCT01922089: Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients
Official title: A Multicenter, Randomized, Double-blind, Parallel Group Study to Assess the Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients Comparing Two Titration Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Heart failure, reduced ejection fraction, LCZ696, titration, safety, tolerability
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-08-14
Enrollment: 498
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of initiating LCZ696 in heart failure patients with reduced ejection fraction (HF-rEF) using conservative (reaching target dose over 6 weeks) and condensed (reaching target dose over 3 weeks) up-titration regimens.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years; CHF with New York Heart Association class II-IV; left ventricular ejection fraction ≤ 35%; on beta blockers

Exclusion Criteria:

* Potassium \> 5.2 mmol/l; estimated glomerular filtration rate \< 30 ml/min/1.73 m2; systolic blood pressure \<100 mmHg or \> 180 mmHg; history of intolerance to recommended target doses of angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)
timeFrame: 12 weeks
measure: Number of Participants Who Tolerated Study Medication for at Least the Last Two Weeks of the Study and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low).
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Novartis Investigative Site
state: Alaska
city: Gilbert
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Torrance
country: United States
facility: Novartis Investigative Site
state: California
city: Atlantis
country: United States
facility: Novartis Investigative Site
state: Florida
city: Chiefland
country: United States
facility: Novartis Investigative Site
state: Florida
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Peoria
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Evansville
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Slidell
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: St. Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Buffalo
country: United States
facility: Novartis Investigative Site
state: New York
city: Laurelton
country: United States
facility: Novartis Investigative Site
state: New York
city: Marion
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oak Ridge
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Livingston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Gabrovo
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Smolian
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Jyvaskyla
country: Finland
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Bad Krozingen
country: Germany
facility: Novartis Investigative Site
city: Berlin-Buch
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dietzenbach
country: Germany
facility: Novartis Investigative Site
city: Ebersbach
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Göttingen
country: Germany
facility: Novartis Investigative Site
city: Hassloch
country: Germany
facility: Novartis Investigative Site
city: Huy / OT Anderbeck
country: Germany
facility: Novartis Investigative Site
city: Ingelheim
country: Germany
facility: Novartis Investigative Site
city: Kelkheim
country: Germany
facility: Novartis Investigative Site
city: Kleve
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mühlheim
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Straubing
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Mosonmagyarovar
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyháza
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
city: Aosta
country: Italy
facility: Novartis Investigative Site
state: AO
city: Cortona
country: Italy
facility: Novartis Investigative Site
state: AR
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Albano Laziale
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Sassari
country: Italy
facility: Novartis Investigative Site
state: SS
city: Vittorio Veneto
country: Italy
facility: Novartis Investigative Site
state: TV
city: San Daniele Del Friuli
country: Italy
facility: Novartis Investigative Site
state: UD
city: San Juan
country: Puerto Rico
facility: Novartis Investigative Site
city: Brezno
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Nitra
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Svidnik
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: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Lucenec
country: Slovakia
facility: Novartis Investigative Site
city: Nove Zamky
country: Slovakia
facility: Novartis Investigative Site
city: Trebisov
country: Slovakia
facility: Novartis Investigative Site
city: Almeria
country: Spain
facility: Novartis Investigative Site
state: Andalucia
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: Villamartin
country: Spain
facility: Novartis Investigative Site
state: Cadiz
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Haydarpasa/Istanbul
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: Dorchester
country: United Kingdom
facility: Novartis Investigative Site
state: Dorset
city: St Leonards on Sea
country: United Kingdom
facility: Novartis Investigative Site
state: East Sussex
city: Oldham
country: United Kingdom
facility: Novartis Investigative Site
state: Lancashire
city: Gateshead
country: United Kingdom
facility: Novartis Investigative Site
state: Tyne and Wear
city: Bath
country: United Kingdom
facility: Novartis Investigative Site
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
city: Coventry
country: United Kingdom
facility: Novartis Investigative Site
city: Harrow
country: United Kingdom
facility: Novartis Investigative Site
city: Nuneaton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Senni M, McMurray JJV, Wachter R, McIntyre HF, Anand IS, Duino V, Sarkar A, Shi V, Charney A. Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study. Eur J Heart Fail. 2018 Mar;20(3):491-500. doi: 10.1002/ejhf.1054. Epub 2017 Nov 22.
citation: Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep;18(9):1193-202. doi: 10.1002/ejhf.548. Epub 2016 May 12.