A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Efficacy of PCSK-9 Inhibitors in Delaying the Progression of Calcified Aortic Valve Disease

NCT06996223 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: NFEC-2025-177
• Study Type: interventional
• Target: 316
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this clinical trial is to understand whether the drug PCSK9 inhibitor can slow the progression of calcific aortic valve disease and to understand the safety of the drug. The primary objective of the study was to evaluate whether PCSK9 inhibitors could delay the progression of aortic stenosis in patients with aortic stenosis. Secondary objectives: 1) To evaluate whether PCSK9 inhibitors can delay the progression of valve calcification in patients with aortic stenosis;2) To evaluate whether PCSK9 inhibitors can reduce long-term adverse events in patients with aortic stenosis;3) To evaluate the effect of PCSK9 inhibitors on circulating Lp(a) levels in patients with aortic stenosis.

Conditions

Aortic Stenosis; PCSK9 Inhibitor; Calcified Aortic Valve Disease

Outcome Measures

Primary Outcomes (1)

• Mean annual variation of peak aortic valve velocity

  Mean annual change in peak aortic valve velocity measured by cardiac ultrasound.

  Baseline ,6 months,12months,24months,36months,48months,

Study Arms (2)

Group A

EXPERIMENTAL

Subjects randomized to the group A will be treated with a lipid-lowering regimen based on PCSK9 inhibitors (subcutaneous injection, twice a week) + statins (maximum tolerated dose). The study lasted for 4 years, and the patients were followed up at 1, 6, 12, 24, 36, and 48 months to assess the efficacy and safety of the drug administration and to collect information on relevant examinations and tests.

Drug: The Group A received PCSK9 inhibitor plus statin therapy

Group B

NO INTERVENTION

Subjects randomized to the B group will be treated with a lipid-lowering regimen based on statins (the maximum tolerated dose). The study lasted for 4 years, and the patients were followed up at 1, 6, 12, 24, 36, and 48 months to assess the efficacy and safety of the drug administration and to collect information on relevant examinations and tests.

Interventions

The Group A received PCSK9 inhibitor plus statin therapy DRUG

Subjects randomized to the Group A will be treated with a lipid-lowering regimen based on PCSK9 inhibitors (subcutaneous injection, twice a week) + statins (maximum tolerated dose).

Group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign informed consent;
• Age ≥18 years old, gender unlimited;
• Patients with aortic stenosis diagnosed by echocardiography;
• Combined with atherosclerotic cardiovascular disease or
• hypercholesterolemia LDL-C≥4.9mmol/L;
• The blood lipids were not up to standard after the maximum tolerated dose of statins;

You may not qualify if:

• Rheumatic aortic stenosis;
• Previous use of PCSK9 inhibitors or allergy to PCSK9 inhibitors;
• Left ventricular ejection fraction ≤35%;
• Patients planned to undergo aortic valve replacement or TAVR in the near future;
• Complicated with other severe valvular diseases;
• Poor adherence to treatment and inability to take medication according to the trial protocol;
• Pregnant and lactating women;
• Combined with active malignant tumors, severe liver and kidney dysfunction and other life expectancy of less than 1 year;
• Participants who are participating in other interventional clinical studies;
• Patients who were judged by the investigator to be ineligible for participation in the trial

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Central Study Contacts

qingchunzeng zeng Doctoral candidate, chief physician, postdoctoral supervisor

CONTACT

+86 15815838368; qingchunzeng@smu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects randomized to the experimental group will be treated with a lipid-lowering regimen based on PCSK9 inhibitors (subcutaneous injection, twice a week) + statins (maximum tolerated dose). Subjects randomized to the control group will be treated with a lipid-lowering regimen based on statins (the maximum tolerated dose). The study lasted for 4 years, and the patients were followed up at 1, 6, 12, 24, 36, and 48 months to assess the efficacy and safety of the drug administration and to collect information on relevant examinations and tests.

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: June 2025 - June 2029