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

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ClinicalTrials.gov Identifier: NCT02884206
Recruitment Status : Completed
First Posted : August 30, 2016
Last Update Posted : November 3, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Heart Failure (CHF) Drug: LCZ696 Drug: Valsartan Drug: Placebo of LCZ696 Drug: Placebo of Valsartan Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 592 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 23, 2016
Actual Primary Completion Date : May 16, 2022
Actual Study Completion Date : May 16, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arms and Interventions
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Arm Intervention/treatment
Experimental: LCZ696
Patients will receive LCZ696 at 100 mg twice daily during a single-blind treatment run-in period to ensure patients tolerate this medication before they are randomized. Down-titration is not allowed during this period. Patients who are able to tolerate LCZ696 100 mg twice daily are eligible to enter the randomized treatment period. Patients randomized to receive LCZ696 will be given LCZ696 at 200 mg twice daily. Patients will receive randomized study drug for three years.
 Drug: LCZ696
LCZ696 50, 100, and 200 mg tablets taken orally twice daily with matching placebo for valsartan

Drug: Placebo of Valsartan
Placebo to match valsartan 40 mg, 80 mg, and 160 mg tablets
Active Comparator: Valsartan
Patients will receive valsartan at 40mg and/or 80mg twice daily during a single-blind treatment run-in period. Following the run-in period, patients randomized to receive valsartan will be given valsartan at 160 mg twice daily for three years.
 Drug: Valsartan
Valsartan 40, 80, and 160 mg tablets taken orally twice daily with matching placebo for LCZ696

Drug: Placebo of LCZ696
Placebo to match LCZ696 50 mg, 100 mg, and 200 mg tablets


Outcome Measures
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Primary Outcome Measures :
  1. Change from baseline in the CogState Global Cognitive Composite Score (GCCS) [ Time Frame: Baseline, week 156 ]
    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.


Secondary Outcome Measures :
  1. Change from baseline in cortical composite standardized uptake value ratio (SUVr) [ Time Frame: Baseline, week 156 ]
    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.

  2. Change from baseline in individual cognitive domains (memory, executive function, and attention) [ Time Frame: Baseline, week 156 ]
    Specific cognitive domains to be assessed include memory, executive function, and attention. A negative change from baseline will indicate worsening performance.

  3. Change from baseline in the summary score of the instrumental activities of daily living (IADL) [ Time Frame: Baseline, week 156 ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02884206


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02884206    
Other Study ID Numbers: CLCZ696B2320
2016-001254-17 ( EudraCT Number )
First Posted: August 30, 2016    Key Record Dates
Last Update Posted: November 3, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
heart failure
cognition
positron emission tomography
magnetic resonance imaging
 LCZ696
valsartan
Chronic heart failure
CHF
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
Sacubitril and valsartan sodium hydrate drug combination
 Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action