Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients

Heart Failure With Reduced Ejection Fraction Clinical Trial

— TITRATION  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01922089
• Other study ID #: CLCZ696B2228
• Secondary ID: 2013-001835-33
• Status: Completed
• Phase: Phase 2
• First received: August 12, 2013
• Last updated: September 16, 2015
• Start date: November 2013
• Est. completion date: August 2014

Study information

• Verified date: September 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesCanada: Health CanadaCzech Republic: State Institute for Drug ControlSlovak Republic: Ethics CommitteeItaly: Ministry of HealthSpain: Ministry of HealthTurkey: Ministry of HealthBulgaria: Ministry of HealthHungary: Institutional Ethics CommitteeFinland: Ministry of Social Affairs and HealthNorway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• LCZ696
LCZ696 50 mg/100 mg/200 mg bid

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Gabrovo
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Smolian
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Finland	Novartis Investigative Site	Jyvaskyla
Finland	Novartis Investigative Site	Tampere
Germany	Novartis Investigative Site	Bad Krozingen
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	Dietzenbach
Germany	Novartis Investigative Site	Ebersbach
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Hassloch
Germany	Novartis Investigative Site	Huy / OT Anderbeck
Germany	Novartis Investigative Site	Ingelheim
Germany	Novartis Investigative Site	Kelkheim
Germany	Novartis Investigative Site	Kleve
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mühlheim
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Straubing
Germany	Novartis Investigative Site	Wuerzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Mosonmagyarovar
Hungary	Novartis Investigative Site	Nyiregyháza
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szekesfehervar
Italy	Novartis Investigative Site	Albano Laziale	RM
Italy	Novartis Investigative Site	Aosta	AO
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Cortona	AR
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	San Daniele Del Friuli	UD
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Vittorio Veneto	TV
Puerto Rico	Novartis Investigative Site	San Juan
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Brezno	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Lucenec
Slovakia	Novartis Investigative Site	Nitra	Slovak Republic
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Svidnik	Slovak Republic
Slovakia	Novartis Investigative Site	Trebisov
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Almeria	Andalucia
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sanlucar de Barrameda	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Villamartin	Cadiz
Turkey	Novartis Investigative Site	Haydarpasa/Istanbul
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	Bath
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Coventry
United Kingdom	Novartis Investigative Site	Dorchester	Dorset
United Kingdom	Novartis Investigative Site	Gateshead	Tyne and Wear
United Kingdom	Novartis Investigative Site	Harrow
United Kingdom	Novartis Investigative Site	Nuneaton
United Kingdom	Novartis Investigative Site	Oldham	Lancashire
United Kingdom	Novartis Investigative Site	St Leonards on Sea	East Sussex
United States	Novartis Investigative Site	Anaheim	California
United States	Novartis Investigative Site	Anchorage	Alaska
United States	Novartis Investigative Site	Atlantis	Florida
United States	Novartis Investigative Site	Aurora	Illinois
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Chiefland	Florida
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigative Site	Gilbert	Arizona
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Laurelton	New York
United States	Novartis Investigative Site	Livingston	Texas
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Oak Ridge	Tennessee
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Slidell	Louisiana
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Finland,  Germany,  Hungary,  Italy,  Puerto Rico,  Slovakia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)	Participants experiencing hypotension, renal dysfunction, hyperkalemia and angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving = 160 mg of valsartan or = 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)	12 weeks	No
Secondary	Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)	Treatment success was defined as the number of participants who achieved and maintained LCZ696 200 mg bid without any dose interruption or down-titration over 12 weeks and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving = 160 mg of valsartan or = 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)	12 weeks	No
Secondary	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).	Tolerability was assessed as the number of participants who achieved LCZ696 200 mg bid and maintained this dose for at least 2 weeks before study completion, regardless of previous dose interruption or down-titration and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving = 160 mg of valsartan or = 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)	12 weeks	No