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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 )

Tracking Information
First Submitted Date  ICMJE August 25, 2016
First Posted Date  ICMJE August 30, 2016
Last Update Posted Date November 3, 2022
Actual Study Start Date  ICMJE November 23, 2016
Actual Primary Completion Date May 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2016)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2016)
  • Change from baseline in a 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Heart Failure (CHF)
Intervention  ICMJE
  • Drug: LCZ696
    LCZ696 50, 100, and 200 mg tablets taken orally twice daily with matching placebo for valsartan
  • 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
  • Drug: Placebo of Valsartan
    Placebo to match valsartan 40 mg, 80 mg, and 160 mg tablets
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: LCZ696
    • Drug: Placebo of Valsartan
  • 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.
    Interventions:
    • Drug: Valsartan
    • Drug: Placebo of LCZ696
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 3, 2020)
592
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2016)
520
Actual Study Completion Date  ICMJE May 16, 2022
Actual Primary Completion Date May 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bulgaria,   Canada,   Croatia,   France,   Germany,   Italy,   Korea, Republic of,   Lithuania,   Netherlands,   Poland,   Russian Federation,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02884206
Other Study ID Numbers  ICMJE CLCZ696B2320
2016-001254-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.

Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP