Vericiguat for the Inhibition of Calcific Aortic Valve Stenosis Progression

Starting soon · Phase 2 · Has a placebo group

Conditions studied: Calcific Aortic Valve Disease, AORTIC VALVE DISEASES, Aortic Valve Stenosis

In brief

Calcific aortic valve stenosis (CAVS) is a condition in which the aortic valve progressively narrows and stiffens due to calcium deposition, eventually impairing blood flow from the heart to the body. No drug therapy has been proven to slow CAVS progression. Individuals with mild-to-moderate CAVS are managed with periodic monitoring until the stenosis becomes severe, at which point surgical or transcatheter valve replacement is the only treatment option. The goal of this clinical trial is to determine whether vericiguat, an oral soluble guanylate cyclase (sGC) stimulator, can slow the progression of mild-to-moderate CAVS. The primary questions this study aims to answer are: Does vericiguat slow the progression of aortic valve calcium accumulation, as measured by the change in aortic valve calcium score from baseline to 24 months, compared to placebo? The study will compare vericiguat against a placebo (an inactive pill that is identical in appearance but contains no active drug). Both participants and the research team will not know which treatment each participant is receiving throughout the study. Participants will: Take vericiguat or placebo orally once daily for 24 months; Begin treatment at 2.5 mg/day and undergo a stepwise dose increase every two weeks to a target dose of 10 mg/day, provided the drug is tolerated; Attend approximately 8 scheduled study visits over two years, during which they will undergo cardiac imaging examinations (transthoracic echocardiography and non-contrast cardiac CT), blood sample collection, physical assessment, and completion of standardized questionnaires on quality of life and heart failure symptoms; Undergo cardiac magnetic resonance imaging (MRI) at the beginning and end of the study, if there are no contraindications. Approximately 238 participants will be enrolled across roughly 19 hospitals in China.

Key facts

Study ID

NCT07715279

Run by

West China Hospital

People needed

238

Starts

2026-08-20

Expected to finish

2029-11-30

Last updated by the study team

2026-07-21

Who can join

Age: 35 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The participant agrees to enter this clinical trial and consents to long-term follow-up;
• 35 ≤ age < 80 years;
• Echocardiographically confirmed mild-to-moderate (peak aortic jet velocity ≥ 2.5 m/s and < 4.0 m/s, aortic valve area > 1.0 cm², and mean aortic valve pressure gradient < 40 mmHg) non-rheumatic aortic valve stenosis;
• Baseline aortic valve calcium score (Agatston score) ≥ 200 AU as measured by cardiac CT;
• Male participants, or female participants who are not of childbearing potential, or female participants who commit to avoiding pregnancy through 4 weeks after the end of the trial.

You may not qualify if…

• Severe aortic stenosis (AS peak velocity ≥ 4.0 m/s, or mean transvalvular aortic pressure gradient ≥ 40 mmHg, or aortic valve area ≤ 1.0 cm², or indexed effective aortic valve area < 0.6 cm²/m²), or very mild stenosis (AS peak velocity < 2.5 m/s), or a planned aortic valvuloplasty/replacement procedure;
• Concomitant severe mitral or tricuspid valve disease (moderate or greater mitral or tricuspid regurgitation, or prior mitral or tricuspid valve repair/valvuloplasty/replacement);
• Concomitant moderate or greater aortic regurgitation;
• Use, within 1 month prior to the screening visit, of medications affecting the NO-sGC-cGMP pathway (e.g., sildenafil, nitrates, etc.), or known hypersensitivity to vericiguat or its components;
• Left ventricular ejection fraction (LVEF) < 50%, or NYHA class III-IV (see Appendix 4 for NYHA classification criteria);
• Presence of a malignancy (except those with an expected cure) or other serious non-cardiac disease with a life expectancy of less than 3 years;
• Rheumatic valvular heart disease;
• Systolic blood pressure (SBP) < 120 mmHg, or a history of symptomatic hypotension, or a history of hemodynamic instability or hypovolemia within the 4 weeks prior to screening;
• Presence of hypertrophic obstructive cardiomyopathy (outflow tract obstruction defined as a peak left ventricular outflow tract pressure gradient ≥ 30 mmHg at rest or after provocative testing);
• Infective endocarditis or complex congenital heart disease;
• Estimated glomerular filtration rate < 15 mL/min/1.73 m², or on dialysis;
• Severe pulmonary disease requiring continuous home oxygen therapy;
• Interstitial lung disease;
• Concomitant disorder of calcium-phosphate metabolism;
• Current use of warfarin;
• ALT and AST ≥ 3 times the upper limit of normal, or severe hepatic insufficiency (e.g., cirrhosis, chronic active liver disease);
• Inability to undergo contrast-enhanced CT, or contrast media allergy;
• Concomitant acute myocarditis, cardiac amyloidosis, cardiac sarcoidosis, or stress (takotsubo) cardiomyopathy;
• Presence of acute coronary syndrome (including unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction) within 60 days prior to randomization, or an indication for coronary revascularization (percutaneous intervention/bypass surgery); or a need for coronary revascularization identified at the time of randomization;
• History of cerebrovascular accident (including TIA or stroke) within 60 days prior to randomization;
• Psychiatric disorder or legal incapacity precluding the ability to provide informed consent;
• Any medical condition, circumstance, or history that, in the investigator's judgment, would compromise the participant's ability to participate in or complete the study.

Full record on ClinicalTrials.gov

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