PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis

NCT07256197 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: PICASO
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aortic Stenosis, Calcific

Keywords

PCSK9 Inhibitors; Calcific Aortic Stenosis

Outcome Measures

Primary Outcomes (1)

• The annualized mean change in peak aortic jet velocity

  The peak aortic jet velocity is measured by echocardiography.

  Up to 24 months

Secondary Outcomes (4)

• The annualized mean change in aortic valve area

  Up to 24 months

• The annualized mean change in aortic valve calcium score

  Up to 24 months

• Cardiac valve surgery

  Up to 24 months

• Change in quality-of-life scores

  Up to 24 months

Other Outcomes (1)

• Safety endpoint

  Up to 24 months

Study Arms (2)

Treatment with PCSK9 inhibitors

EXPERIMENTAL

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

Treatment without PCSK9 inhibitors

OTHER

Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.

Other: Treatment without PCSK9 inhibitors

Interventions

Treatment with PCSK9 inhibitors DRUG

Patients in experimental group are treated with PCSK9 inhibitors (Tafolecimab subcutaneously every two weeks) plus guideline-directed management in cardiovascular primary or secondary prevention.

Also known as: Treatment with Proprotein convertase subtilisin/kexin type 9 inhibitors

Treatment with PCSK9 inhibitors

Treatment without PCSK9 inhibitors OTHER

Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.

Also known as: Treatment without Proprotein convertase subtilisin/kexin type 9 inhibitors

Treatment without PCSK9 inhibitors

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;
• 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).

You may not qualify if:

• Any previous treatment with PCSK9 inhibitors;
• Patients must be treated with PCSK9 inhibitors by physician's judgment;
• Patients who cannot maintain PCSK9 inhibitor use for 24 months;
• Contraindications or hypersensitivity to PCSK9 inhibitors;
• Suspected or confirmed familial hypercholesterolemia;
• Fasting triglycerides (TG) \>400 mg/dL (4.5 mmol/L) at baseline screening;
• Thyroid hypofunction;
• Active or chronic liver disease;
• Severe renal insufficiency (eGFR \<30 mL/min/1.73 m²);
• History of intracranial hemorrhage;
• History of alcohol or drug abuse；
• Known active infection, or severe hematologic, metabolic, or endocrine dysfunction;
• Systemic corticosteroid or cyclosporine therapy within the past 3 months;
• Active malignancy;
• Any life-threatening condition with life expectancy less than 12 months;

Sponsors & Collaborators

• Beijing Luhe Hospital: collaborator
• Beijing Jishuitan Hospital: collaborator
• Chinese Academy of Medical Sciences, Fuwai Hospital: collaborator
• Beijing Hospital: collaborator
• Nanchong Central Hospital: collaborator
• Peking University First Hospital: collaborator
• Beijing Anzhen Hospital: lead

Study Sites (1)

Beijing Anzhen Hospital, Capital Medical University

Beijing, Beijing Municipality, 100029, China

Location

Related Publications (35)

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MeSH Terms

Conditions

Aortic Valve, Calcification of

Interventions

Therapeutics; PCSK9 Inhibitors

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Zhijian Wang

  Beijing Anzhen Hospital

  STUDY CHAIR

• Xiaoteng Ma

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhijian Wang

CONTACT

+8615711057972; zjwang1975@hotmail.com

Xiaoteng Ma

CONTACT

+8618810616459; maxiaotengai@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 1, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: April 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)