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.
ID
Source
Brief title
Condition
- Heart failures
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
To evaluate the effect of LCZ696 compared to valsartan on amyloid deposition in
the brain in a subset of patients using positron emission Tomography amyloid
(PET) imaging over 3 years.
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
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.
Background summary
Cognitive impairment has been reported in patients with heart failure in
several studies. Prevalence observed ranged from 25-75% within these studies.
Changes in cognition due to improved hart function has not yet been evaluated
extensively. In observational studies a connection was shown between congitive
impairment and elevated blood pressure. Also correlation between cognitive
impairment at the age of 70 and the development of dementia 10-20 years later
was shown.
It would be possible that improvement of the heart function and blood pressure,
due to a long term treatment of LCZ696 can result in a improvement of the
cognition.
Also, in this study the effect of the NEP-inhibitor component to the existence
of Amyloid-beta, which might be a factor in developing Alzheimers' disease.
This has not been found in the Paradigm-HFstudy.
In this study beta-amyloid plaquea will be investigated by MRI/PETscans.
Study 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.
Study design
Multi-center, randomized, double-blind, parallel group phase Ill study with
active comparator.
Screening period of up to 2 weeks. Single-blind, run-in period 3-8 weeks
(treatment with LCZ696 and valsartan separately).
Thereafter randomization (1:1) to:
1. LCZ696 200 mg bid,
2. Valsartan 160 mg bid.
Back-titration if dose is not tolerated.
Continuation of regular treatment against heart failure (except ACE-,
angiotensin - and renin inhibitors).
Total study duration 38 months (including screening/run-in).
Intervention
Treatment with LCZ696 or valsartan.
Study burden and risks
Risks are the radiation (3x natural radiation amount), possible AEs due to the
IMP and burden study procedures.
- Physical examination: 10 x
- Vital signs: 12 x
- Weight: 8 x
- Bloodtests: 11 x
- Echocardiogram: 1 x
- MRI: max 3 x
- PET scan: 3 x
- Cogstate: 9 x
- Completion of PROs: 9 x
During study, forbidden co-medication.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
- Male or female patients aged >= 60 years of age.
- Chronic heart failure with current symptom(s) (NYHA class II-IV) at Screening
visit.
- 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.
- Patiens with at least 1 of the following:
- prior HF hospitalisation in 12 months prior to screening visit
- NT-proBNP > 125 pg/ml at screening visit.
- 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.
See protocol for more details.
Exclusion criteria
- Current acute decompensated HF requiring therapy
- Acute coronary syndrome, cardiac surgery, other major CV surgery, urgent PCI,
carotid surgery/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 who require treatment with 2 or more of the following: an ACEi, an
ARB or a renin inhibitor.
- MMSE score < 24 at Screening visit
- 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).
- Inability to perform tests based on significant motor or sensory skill.
See protocol for details and more exclusion criteria
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001254-17-NL |
| ClinicalTrials.gov | NCT02884206 |
| CCMO | NL60363.029.17 |