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PCSK9 Inhibitors in the Progression of Aortic Stenosis

Phase 2
Conditions
Aortic Valve Stenosis
Interventions
Drug: Placebos
Drug: PCSK9 Inhibitor [EPC]
Registration Number
NCT03051360
Lead Sponsor
Seoul National University Hospital
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
140
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebosPatients will receive bi-weekly placebo.
PCSK9 inhibitorPCSK9 Inhibitor [EPC]Patients will receive bi-weekly PCSK9 inhibitor .
Primary Outcome Measures
NameTimeMethod
Progression of the Calcium score measured by cardiac CT (Agatston score) and by NaF PET2 years

Calcium score progression in the PCSK9 inhibitor group and placebo group

Secondary Outcome Measures
NameTimeMethod
Mean change in Lp(a) levels between treatment arms2 years

Lp(a) levels will be measured in blood chemistry

Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level2 years

Lipid panels will be measured in blood chemistry

Any myocardial infarction event2 years
Any revascularization for coronary artery disease2 years
Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs2 years
Aortic valve peak velocity measured by echocardiography2 years
Any cardiac death event2 years
Aortic valve area measured by echocardiography2 years
Any death event2 years

Trial Locations

Locations (1)

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

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