PCSK9 Inhibitors in the Progression of Aortic Stenosis

Proprotein Convertase Subtilisin Kexin Type 9 Inhibitor in Aortic Stenosis

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.

Study Overview

• Status: Unknown
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: PCSK9 Inhibitor [EPC]; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyo-Soo Kim, MD, PhD; Phone Number: +82-2- 2072-2226; Email: hyosoo@snu.ac.kr
• Study Contact Backup: Name: Jeehoon Kang, MD; Phone Number: +82-10-2416-2406; Email: medikang@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
    • Contact: Hyo-Soo Kim, MD, PhD; Phone Number: +82-2- 2072-2226; Email: hyosoo@snu.ac.kr
    • Contact: Jeehoon Kang, MD; Phone Number: +82-10-2416-2406; Email: medikang@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PCSK9 inhibitor; Patients will receive bi-weekly PCSK9 inhibitor .	Drug: PCSK9 Inhibitor [EPC]; Patients will receive PCSK9 inhibitor by a biweekly injection
Placebo Comparator: Placebo; Patients will receive bi-weekly placebo.	Drug: Placebos; Patients will receive Placebo by a biweekly injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs		2 years
Mean change in Lp(a) levels between treatment arms	Lp(a) levels will be measured in blood chemistry	2 years
Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level	Lipid panels will be measured in blood chemistry	2 years
Aortic valve area measured by echocardiography		2 years
Aortic valve peak velocity measured by echocardiography		2 years
Any death event		2 years
Any cardiac death event		2 years
Any myocardial infarction event		2 years
Any revascularization for coronary artery disease		2 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: January 23, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 13, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: aortic valve stenosis; PCSK9 inhibitor
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: PCSK9 AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No