Aortic Valve Stenosis
Conditions
Keywords
aortic valve stenosis, PCSK9 inhibitor
Brief summary
Investigators plan evaluate whether PCSK9 inhibitors, a medication that can lower lipoprotein(a) and control dyslipidemia, can inhibit the progression of aortic stenosis, through a randomized controlled trial.
Detailed description
Aortic valve disease is the most common form of heart valve disease and is a major burden to society. Aortic valve disease is also expected to become more prevalent with the aging. Among aortic diseases, 'aortic stenosis (AS)', which is a narrowing of the aortic valve, and leads to symptoms of heart failure and sometimes death. For treatment of AS, the valve in replaced in a surgical to percutaneous method. Regardless of the method, valve replacement has its potential costs and complications that is an important issue that needs to be solved. Therefore, controlling the progression of AS and increasing the efficacy of medical therapy before valvular replacement is needed, is an important medico-social problem. Regarding the pathophysiology of AS, an elevation of lipoprotein(a) and dyslipidemia have been reported to be associated with the progression of cardiovascular calcification. PCSK9 inhibitors, which is a medication that can control both lipoprotein(a) and dyslipidemia may be a effective medication to control the progression of AS. Therefore, investigators will perform a randomized control trial, to compare the effect of PCSK9 inhibitors vs. placebo in its influence to AS progression.
Interventions
Patients will receive PCSK9 inhibitor by a biweekly injection
DRUGPlacebos
Patients will receive Placebo by a biweekly injection
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Prospective, Double blind, Multi-center, Randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient agrees to participate in this study by signing the informed consent form. Alternatively, a legally authorized patient representative may agree to the patient's participation in this study and sign the informed consent form. 2. The patient has a working diagnosis of aortic stenosis (mild to moderate), and has fair treatment compliance.
Exclusion criteria
1. Age under 19 years old 2. Hypersensitivity to PCSK9 inhibitor 3. LDL cholesterol \< 70mg/dL at baseline 4. Poor treatement compliance (The patient will need to visit the out-patient clinic every 2-weeks for medication) 5. Positive pregnancy test or is known to be pregnant 6. Any other reason the investigator deems the subject to be unsuitable for the study (e.g., Active malignant tumor, Any life-threatening condition with life expectancy less than 6months, etc.) 7. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of the Calcium score measured by cardiac CT (Agatston score) and by NaF PET | 2 years | Calcium score progression in the PCSK9 inhibitor group and placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in Lp(a) levels between treatment arms | 2 years | Lp(a) levels will be measured in blood chemistry |
| Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level | 2 years | Lipid panels will be measured in blood chemistry |
| Aortic valve area measured by echocardiography | 2 years | — |
| Aortic valve peak velocity measured by echocardiography | 2 years | — |
| Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs | 2 years | — |
| Any cardiac death event | 2 years | — |
| Any myocardial infarction event | 2 years | — |
| Any revascularization for coronary artery disease | 2 years | — |
| Any death event | 2 years | — |
Countries
South Korea
Contacts
Primary ContactHyo-Soo Kim, MD, PhD
Backup ContactJeehoon Kang, MD
Outcome results
None listed