PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis (PICASO)

March 29, 2026 updated by: Zhi Jian Wang, Beijing Anzhen Hospital

Effect and Safety of PCSK9 Inhibitors on the Progression of Mild/Middle Calcific Aortic Stenosis: A Randomized Controlled Clinical Trial

Calcific aortic stenosis (CAS) can cause severe adverse cardiac events, but there are currently no effective drugs that can prevent or delay the progression of the disease. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Calcific aortic stenosis (CAS) can cause severe adverse cardiac events, but there are currently no effective drugs that can prevent or delay the progression of the disease. In fact, aortic valve replacement remains the only treatment option. CAS has been shown to be associated with Lp(a), LDL-C and PCSK9. Several observational studies indicated that the use of statins to decrease LDL-C levels was associated with the reduced incidence of CAS, but no randomized controlled trials (RCTs) showd that statins had any benefit on the progression of CAS. This may be related to the limited reduction of LDL-C by statin therapy. The PCSK9 inhibitors have emerged as a new lipid-lowering drug. On the basis of statin therapy, PCSK9 inhibitors can further reduce LDL-C and Lp(a) levels by 50% to 60% and 20% to 30%, respectively. Some studies reported that elevated plasma PCSK9 levels were related to CAS and PCSK9 R46L loss-of-function mutation was associated with lower rates of CAS, and importantly, some observational studies found that PCSK9 inhibitors could reduce the incidence of CAS. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS. A total of 160 patients with mild or moderate CAS not currently requiring valve replacement therapy will be enrolled and randomized (stratified by center) in a 1:1 ratio to two groups, the PCSK9 inhibitor treatment group (test group) or the no PCSK9 inhibitor group (control group). All patients will be followed for at least 2 years after randomization. After enrollment, telephone follow-ups will be conducted in the first month and every three months to collect data including medication use, quality-of-life scores, and clinical endpoint events. Doppler echocardiography will be collected at baseline, the 1-year visit, the 2-year visit, and before study withdrawal. Blood samples and aortic computed tomography angiography (CTA) will be collected at baseline, the 2-year visit, and before study withdrawal. The primary endpoint is the annualized mean change in peak aortic jet velocity over the 24-month follow-up period. Secondary endpoints include the annualized mean change in aortic valve area by echocardiography, the annualized mean change in aortic valve calcium score by aortic CTA, the incidence of cardiac valve surgery, and changes in quality-of-life scores. The safety endpoint is a composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. The results of this trial will provide new insights into the treatment of CAS patients.

Blood samples should be tested for serological indicators, including blood routine, C-reactive protein (CRP), biochemical, coagulation function, brain natriuretic peptide (BNP), markers of myocardial injury, glycosylated hemoglobin, erythrocyte sedimentation rate, cytokines (12 items).

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100029
        • Beijing AnZhen Hospital, Capital Medical University
        • Principal Investigator:
          • Zhijian Wang
        • Contact:
        • Sub-Investigator:
          • Xiaoteng Ma

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged 18-85 years old, clinically diagnosed with mild or moderate CAVS (echocardiography shows ejection fraction > 50%; valve orifice area > 1.0 cm²; left ventricular stroke volume index > 35 ml/m²; flow velocity ≥ 2 m/s and < 4 m/s, or mean transvalvular pressure gradient < 40 mmHg) and currently not requiring valve replacement therapy;
  2. LDL-C ≥ 2.6 and < 4.9 mmol/L, or Lp(a) ≥ 30 mg/dL, or receiving statin therapy due to a clinical diagnosis of hypercholesterolemia/hyperlipidemia;

  3. Patients who can understand the purpose of the trial, voluntarily participate, sign the informed consent form, and are willing to undergo clinical follow-up in accordance with the trial requirements.

    • The position and method of measurement have been further clarified in ultrasonic measurement to ensure comparability among all enrolled patients, as follows: Aortic valve peak flow velocity, aortic valve mean pressure gradient, and valve orifice area (select images of at least 3 consecutive cardiac cycles with stable heart rate; for atrial fibrillation, select images of more than 5 consecutive cardiac cycles; obtain the peak blood flow velocity of the aortic valve orifice using continuous wave Doppler in the apical 5-chamber view; calculate the instantaneous aortic valve pressure gradient using the simplified Bernoulli equation, and calculate the standardized aortic valve orifice area using the continuity equation; all participating sonographers will receive unified training, perform measurements in fixed views and retain images, which will then be reviewed by two experienced sonographers who are blinded to the trial in the core laboratory).

Exclusion Criteria:

  1. Any previous treatment with PCSK9 inhibitors;
  2. Patients must be treated with PCSK9 inhibitors by physician's judgment;
  3. Patients who cannot maintain PCSK9 inhibitor use for 24 months;
  4. Contraindications or hypersensitivity to PCSK9 inhibitors;
  5. Suspected or confirmed familial hypercholesterolemia;
  6. Fasting triglycerides (TG) >400 mg/dL (4.5 mmol/L) at baseline screening;
  7. Thyroid hypofunction;
  8. Active or chronic liver disease;
  9. Severe renal insufficiency (eGFR <30 mL/min/1.73 m²);
  10. History of intracranial hemorrhage;
  11. History of alcohol or drug abuse；
  12. Known active infection, or severe hematologic, metabolic, or endocrine dysfunction;
  13. Systemic corticosteroid or cyclosporine therapy within the past 3 months;
  14. Active malignancy;
  15. Any life-threatening condition with life expectancy less than 12 months;
  16. Rheumatic aortic stenosis;
  17. Severe mitral stenosis (mitral valve area <1 cm²);
  18. Severe mitral or aortic regurgitation;
  19. Planned cardiac valve surgery;
  20. Left ventricular ejection fraction < 30% or severe heart failure (NYHA class III or IV);
  21. Implanted permanent pacemaker or cardioverter-defibrillator;
  22. Drug-refractory arrhythmias;
  23. Pregnancy, lactation, or planned pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment with PCSK9 inhibitors
Patients in experimental group are treated with PCSK9 inhibitors (150mg Tafolecimab subcutaneously every two weeks) and guideline-directed management in cardiovascular primary or secondary prevention.
Drug: Treatment with PCSK9 inhibitors
Patients in experimental group are treated with PCSK9 inhibitors (Tafolecimab subcutaneously every two weeks) plus guideline-directed management in cardiovascular primary or secondary prevention.
Other Names:
  • Treatment with Proprotein convertase subtilisin/kexin type 9 inhibitors
Other: Treatment without PCSK9 inhibitors
Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.
Other: Treatment without PCSK9 inhibitors
Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.
Other Names:
  • Treatment without Proprotein convertase subtilisin/kexin type 9 inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The annualized mean change in peak aortic jet velocity
Time Frame: Up to 24 months
The peak aortic jet velocity is measured by echocardiography.
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in quality-of-life scores
Time Frame: Up to 24 months
Change in quality-of-life scores is assessed with the use of the EQ-5D-3L scale
Up to 24 months
The annualized mean change in aortic valve area
Time Frame: Up to 24 months
The aortic valve area is measured by echocardiography.
Up to 24 months
The annualized mean change in aortic valve calcium score
Time Frame: Up to 24 months
The aortic valve calcification score is measured by aortic computed tomography angiography.
Up to 24 months
Cardiac valve surgery
Time Frame: Up to 24 months
Transcatheter aortic valve implantation or surgical aortic valve replacement
Up to 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety endpoint
Time Frame: Up to 24 months
The safety endpoint is a composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Anzhen Hospital

Collaborators

Peking University First Hospital
Beijing Hospital
Chinese Academy of Medical Sciences, Fuwai Hospital
Beijing Jishuitan Hospital
Beijing Luhe Hospital
Nanchong Central Hospital

Investigators

  • Study Chair: Zhijian Wang, Beijing Anzhen Hospital
  • Principal Investigator: Xiaoteng Ma, Beijing Anzhen Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

January 31, 2029

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

November 20, 2025

First Posted (Actual)

December 1, 2025

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 29, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PICASO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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