Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction

Chronic Heart Failure (CHF) Clinical Trial

— PERSPECTIVE  

Official title:

A Multicenter, Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02884206
• Other study ID #: CLCZ696B2320
• Secondary ID: 2016-001254-17
• Status: Completed
• Phase: Phase 3
• Start date: November 23, 2016
• Est. completion date: May 16, 2022

Study information

• Verified date: November 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of LCZ696 compared to valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction. Cognitive function will be assessed using a comprehensive battery of tests with an evaluation of longitudinal change of cognitive domains including memory, executive function, and attention.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 592
• Est. completion date: May 16, 2022
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Key Inclusion Criteria:

• Chronic heart failure with current symptoms NYHA class II-IV

• Left ventricular ejection fraction > 40%

• NT-proBNP >= 125 pg/mL at screening visit

• Patient with evidence of adequate functioning to complete study assessments

Key Exclusion Criteria:

• Patients with acute decompensated heart failure requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs

• Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major CV surgery, or urgent percutaneous coronary intervention (PCI), carotid surgery or carotid angioplasty, history of stroke or transient ischemic attack within the 3 months prior to Screening visit or an elective PCI within 30 days prior to Screening visit

• Patients with history of hereditary or idiopathic angioedema or angioedema related to previous ACEi or ARB therapies

• Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor

• Patients with one of the following:

1. Patients with serum potassium >5.2 mmol/L (mEq/L) at Screening visit

2. Patients with serum potassium >5.4 mmol/L (mEq/L) at any visit during run-in treatment period or at randomization visit

3. Systolic blood pressure (SBP) =180 mmHg at Screening visit, or

4. SBP <110 mmHg at Screening visit, or

5. SBP <100 mmHg or symptomatic hypotension as determined by the investigator at Visit 103 or at randomization visit

6. Body mass index (BMI) >45 kg/m^2

• Patients with

1. known pericardial constriction, genetic hypertrophic cardiomyopathy, infiltrative cardiomyopathy

2. hemodynamically significant obstructive valvular disease

• Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 beats per minute

• Inability to perform cognitive battery or other study evaluations based on significant motor (e.g. hemiplegia, muscular-skeletal injury) or sensory (blindness, decreased or uncorrected visual or auditory acuity) skill

• Clinically significant cerebral pathology for example large cerebral aneurysm or space occupying lesion that may impact cognition as assessed by central MRI reader

• Mini mental state examination score less than 24 at screening

• Patients with a clinical diagnosis of Alzheimer's disease or other dementia syndromes or any indication for or current treatment with cholinesterase inhibitors and/or another prescription AD treatment (e.g. memantine).

Related Conditions & MeSH terms

• Chronic Heart Failure (CHF)
• Heart Failure

Intervention

Drug:
• LCZ696
LCZ696 50, 100, and 200 mg tablets taken orally twice daily with matching placebo for valsartan
• Valsartan
Valsartan 40, 80, and 160 mg tablets taken orally twice daily with matching placebo for LCZ696
• Placebo of LCZ696
Placebo to match LCZ696 50 mg, 100 mg, and 200 mg tablets
• Placebo of Valsartan
Placebo to match valsartan 40 mg, 80 mg, and 160 mg tablets

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires	ARG
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Capital Federal
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Ramos Mejia	Buenos Aires
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Chemside	Queensland
Australia	Novartis Investigative Site	Geelong	Victoria
Australia	Novartis Investigative Site	Milton	Queensland
Belgium	Novartis Investigative Site	Aalst
Bulgaria	Novartis Investigative Site	Sofia	BGR
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Hamilton	Ontario
Croatia	Novartis Investigative Site	Rijeka
Croatia	Novartis Investigative Site	Zagreb
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Tourcoing
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	Bitburg
Germany	Novartis Investigative Site	Dessau-Roßlau
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden	Sachsen
Germany	Novartis Investigative Site	Elsterwerda
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Wuppertal
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pozzilli	IS
Italy	Novartis Investigative Site	Rozzano	MI
Korea, Republic of	Novartis Investigative Site	Seongnam Si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-Do
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Vilnius
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Hertogenbosch
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow	Maloposkie
Poland	Novartis Investigative Site	Lodz	Lodzkie
Poland	Novartis Investigative Site	Tarnow	Malopolskie
Poland	Novartis Investigative Site	Warszawa
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	Saratov
Russian Federation	Novartis Investigative Site	St Petersburg
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	San Sebastian de los Reyes	Madrid
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Zaragoza
Switzerland	Novartis Investigative Site	Basel
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Meselik	Eskisehir
Turkey	Novartis Investigative Site	Sivas
United Kingdom	Novartis Investigative Site	Axbridge	Somerset
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bournemouth
United Kingdom	Novartis Investigative Site	Cardiff	Wales
United Kingdom	Novartis Investigative Site	East Yorkshire
United Kingdom	Novartis Investigative Site	Harrow
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	Newport
United Kingdom	Novartis Investigative Site	Stevenage
United States	Novartis Investigative Site	Andalusia	Alabama
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Danbury	Connecticut
United States	Novartis Investigative Site	Edgewater	Florida
United States	Novartis Investigative Site	Elmer	New Jersey
United States	Novartis Investigative Site	Eunice	Louisiana
United States	Novartis Investigative Site	Fort Mill	South Carolina
United States	Novartis Investigative Site	Fresno	California
United States	Novartis Investigative Site	Gastonia	North Carolina
United States	Novartis Investigative Site	Glendale	Arizona
United States	Novartis Investigative Site	Gonzales	Texas
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Homestead	Florida
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Inverness	Florida
United States	Novartis Investigative Site	Jacksonville Beach	Florida
United States	Novartis Investigative Site	Kalispell	Montana
United States	Novartis Investigative Site	Loma Linda	California
United States	Novartis Investigative Site	Lombard	Illinois
United States	Novartis Investigative Site	Long Beach	California
United States	Novartis Investigative Site	Lufkin	Texas
United States	Novartis Investigative Site	Mesa	Arizona
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Naples	Florida
United States	Novartis Investigative Site	Newport Beach	California
United States	Novartis Investigative Site	Oregon City	Oregon
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	Rock Hill	South Carolina
United States	Novartis Investigative Site	Saginaw	Michigan
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Santa Ana	California
United States	Novartis Investigative Site	Santa Ana	California
United States	Novartis Investigative Site	Springfield	Oregon
United States	Novartis Investigative Site	Springfield	Illinois
United States	Novartis Investigative Site	Summerville	South Carolina
United States	Novartis Investigative Site	Sun City West	Arizona
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Topeka	Kansas
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,  Argentina,  Australia,  Belgium,  Bulgaria,  Canada,  Croatia,  France,  Germany,  Italy,  Korea, Republic of,  Lithuania,  Netherlands,  Poland,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the CogState Global Cognitive Composite Score (GCCS)	Change in cognition is assessed as a change in a Global Cognitive Composite Z score. The cognitive composite comprises cognitive domains including attention, memory, and executive function. A negative change from baseline will indicate worsening performance.	Baseline, week 156
Secondary	Change from baseline in cortical composite standardized uptake value ratio (SUVr)	Changes in amyloid plaque deposition over time will be assessed using florbetapir-18F. The longitudinal change in the standardized uptake value ratio will be determined.	Baseline, week 156
Secondary	Change from baseline in individual cognitive domains (memory, executive function, and attention)	Specific cognitive domains to be assessed include memory, executive function, and attention. A negative change from baseline will indicate worsening performance.	Baseline, week 156
Secondary	Change from baseline in the summary score of the instrumental activities of daily living (IADL)	Instrumental activities of daily living will be assessed using the functional activities questionnaire. The functional activities questionnaire will be used as a standardized assessment of activities of daily living. This questionnaire is typically used to distinguish normal subjects from subjects with mild to moderate cognitive impairment. The test is made up of 10 questions that reflect a subject's ability to perform activities of daily living and to function independently. Test scores range from 0 to 30, a score of 0 is completely normal where as a higher score denotes impairment. Each of 10 questions is scored from 0, representing normal to 3, dependent on someone else to perform the activity. A negative change from baseline denotes improvement.	Baseline, week 156