PCSK9 Inhibitors in the Progression of Aortic Stenosis

Aortic Valve Stenosis Clinical Trial

Official title:

Proprotein Convertase Subtilisin Kexin Type 9 Inhibitor in Aortic Stenosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03051360
• Other study ID #: PCSK9 AS
• Status: Not yet recruiting
• Phase: Phase 2
• First received: January 23, 2017
• Last updated: February 8, 2017
• Start date: June 1, 2017
• Est. completion date: January 1, 2020

Study information

• Verified date: February 2017
• Source: Seoul National University Hospital
• Contact: Hyo-Soo Kim, MD, PhD
• Phone: +82-2- 2072-2226
• Email: hyosoo[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: January 1, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Drug:
• PCSK9 Inhibitor [EPC]
Patients will receive PCSK9 inhibitor by a biweekly injection
• Placebos
Patients will receive Placebo by a biweekly injection

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of the Calcium score measured by cardiac CT (Agatston score) and by NaF PET	Calcium score progression in the PCSK9 inhibitor group and placebo group	2 years
Secondary	Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs		2 years
Secondary	Mean change in Lp(a) levels between treatment arms	Lp(a) levels will be measured in blood chemistry	2 years
Secondary	Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level	Lipid panels will be measured in blood chemistry	2 years
Secondary	Aortic valve area measured by echocardiography		2 years
Secondary	Aortic valve peak velocity measured by echocardiography		2 years
Secondary	Any death event		2 years
Secondary	Any cardiac death event		2 years
Secondary	Any myocardial infarction event		2 years
Secondary	Any revascularization for coronary artery disease		2 years