Studio per valutare gli effetti di LCZ696 sulla funzione cognitiva in pazienti con scompenso cardiaco cronico a frazione di eiezione preservata
- Conditions
- Heart Failure with preserved ejection fraction (HF-pEF)MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-001254-17-IT
- Lead Sponsor
- OVARTIS PHARMA SERVICES AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 592
1. Written informed consent including consent for APOE4 gene testing must be obtained before any assessment is performed
2. Male or female patients aged = 60 years of age.
3. Chronic heart failure with current symptom(s) (NYHA class II-IV) at Screening visit.
4. LVEF > 40%
a. By any method using most recent assessment within 6 months prior to screening visit OR
b. By an echocardiogram performed during the screening visit, if previous assessment is not available.
5. NT-proBNP = 125 pg/mL at Screening visit
6. Patient with evidence of adequate functioning (e.g.: intellectual, motor, visual and auditory) to complete the study assessments and has elementary education or 6 years of sustained employment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 445
1. Current acute decompensated HF requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs.
2. Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major cardiovascular (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.
3. Patients with history of hereditary or idiopathic angioedema or angioedema related to previous angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapies.
4. Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor.
5. Patients with one of the following:
a. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) formula at screening visit, or
b. eGFR <25 mL/min/1.73m2 at Visit 103 or at end of run-in / randomization visit, or
c. eGFR reduction >35% (compared to Visit 1) at Visit 103 or Visit 199/201
6. MMSE score <24 at Screening visit
7. 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 Alzheimer's Disease (AD) treatment (e.g., memantine).
8. Any history of medical or neurological condition likely to affect the participant's cognition (e.g., clinically significant brain trauma with loss of consciousness > 3 minutes within 6 months prior to screening, Huntington's disease, Parkinson's disease, Lyme's disease, syphilis, HIV dementia, uncontrolled seizure disorder) or clinically significant abnormalities in thyroid function tests, Vitamin B12 or folate deficiency requiring treatment at screening. (Patients who are adequately treated may be included at investigator discretion).
9. 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.
10. Score yes on item 4 or item 5 of the Suicidal Ideation section of the Columbia suicidality severity rating scale (C-SSRS), if this ideation occurred in the past 6 months, or yes on any item of the Suicidal Behavior section, except for the Non-Suicidal Self-Injurious Behavior (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
11. Clinically significant cerebral pathology, for example large cerebral aneurysm, space occupying lesion etc. that may impact cognition as assessed by MRI central reader.
12. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
13. History or presence of any other disease with a life expectancy of <3 years
14. Women of child bearing potential defined as all women physiologically capable of becoming pregnant.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effects of LCZ696 compared to valsartan on cognitive function over 3 years in patients with HFpEF as assessed by the CogState cognitive assessment battery.;Secondary Objective: To evaluate the effect of LCZ696 compared to valsartan on Beta-amyloid deposition in the brain in a subset of patients using amyloid positron emission tomography (PET) imaging over 3 years.<br>To evaluate the effects of LCZ696 compared to valsartan on individual cognitive domains (memory, executive function, and attention) as assessed by the individual components of the CogState battery over 3 years.<br>To compare LCZ696 to valsartan in evaluating changes in instrumental activities of daily living (IADL) as assessed with Functional Activity Questionnaire (FAQ) over 3 years.;Primary end point(s): Change from baseline to 3 years in the CogState Global Cognitive Composite Score (GCCS);Timepoint(s) of evaluation of this end point: From baseline to 3 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in a cortical composite SUVr (standardized uptake value ratio) at 3 years<br>- Change from baseline in individual cognitive domains (memory, executive function, and attention) as assessed by the individual components of the cognitive assessment battery at 3 years<br>- Change from baseline in the summary score of the instrumental activities of daily living (IADL) as assessed with Functional Activity Questionnaire (FAQ) at 3 years;Timepoint(s) of evaluation of this end point: From baseline to 3 years