Clinical trial NCT03051360: PCSK9 Inhibitors in the Progression of Aortic Stenosis
Official title: Proprotein Convertase Subtilisin Kexin Type 9 Inhibitor in Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Aortic Valve Stenosis
Keywords: aortic valve stenosis
PCSK9 inhibitor
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2017-02-13
Enrollment: 140
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, Double blind, Multi-center, Randomized clinical trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression of the Calcium score measured by cardiac CT (Agatston score) and by NaF PET
timeFrame: 2 years
Secondary outcomes:
measure: Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs
timeFrame: 2 years
measure: Mean change in Lp(a) levels between treatment arms
timeFrame: 2 years
measure: Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level
timeFrame: 2 years
measure: Aortic valve area measured by echocardiography
timeFrame: 2 years
measure: Aortic valve peak velocity measured by echocardiography
timeFrame: 2 years
measure: Any death event
timeFrame: 2 years
measure: Any cardiac death event
timeFrame: 2 years
measure: Any myocardial infarction event
timeFrame: 2 years
measure: Any revascularization for coronary artery disease
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References: