Vericiguat for the Inhibition of Calcific Aortic Valve Stenosis Progression

NCT07715279 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2025-384ChiCTR2500108507
• Study Type: interventional
• Target: 238
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Calcific Aortic Valve Disease; AORTIC VALVE DISEASES; Aortic Valve Stenosis

Keywords

Vericiguat; BAY1021189; Soluble Guanylyl Cyclase; sGC stimulator; sGC activator; Cyclic GMP

Outcome Measures

Primary Outcomes (1)

• Change in Aortic Valve Calcium (AVC) Score at 24 months

  Change in log-transformed aortic valve calcium score from baseline, measured by non-contrast electrocardiographic-gated cardiac CT (Agatston method). Higher scores mean worse outcome.

  At 24 months

Secondary Outcomes (17)

• Hierarchical Composite Endpoint including Time to all-cause death, Time to aortic valve-related clinical events and Change in aortic valve calcification (AVC) score from baseline at 24 months (log-transformed).

  Up to 24 months

• Change in Aortic Valve Calcium (AVC) Score at 12 Months

  At 12 months

• Change from baseline in aortic valve calcium volume

  At 12 and 24 months

• Change in Aortic Valve Peak Velocity

  At 6, 12, 18, and 24 months

• Change in Aortic Valve Mean Pressure Gradient

  At 6, 12, 18, and 24 months

Other Outcomes (3)

• Change in Coronary Artery Calcium Score at 12 and 24 Months

  At 12 and 24 months

• Change in Cardiac Magnetic Resonance Parameters at 24 Months

  At 24 months

• Change in Echocardiographic Left Ventricular Mass Index

  At 6, 12, 18, and 24 months

Study Arms (2)

Vericiguat

ACTIVE COMPARATOR

Vericiguat orally once daily.

Drug: Vericiguat (BAY1021189)

Placebo

PLACEBO COMPARATOR

Matching placebo tablets orally once daily

Drug: Placebo

Interventions

Vericiguat (BAY1021189) DRUG

Vericiguat 2.5 mg orally once daily, titrated every 2 weeks (2.5 mg → 5 mg → 10 mg) to a target maintenance dose of 10 mg once daily. Total treatment duration: 24 months

Also known as: MK-1242, BAY 1021189

Vericiguat

Placebo DRUG

Matching placebo tablets orally once daily, with a dose-titration schedule synchronized to the vericiguat arm to maintain blinding. Placebo tablets are identical to vericiguat tablets (2.5 mg, 5 mg, and 10 mg dose strengths) in size, shape, color, and texture. The same SBP-based dose-adjustment rules are applied. Total treatment duration: 24 months.

Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant agrees to enter this clinical trial and consents to long-term follow-up;
• ≤ 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;

Sponsors & Collaborators

• West China Hospital: lead
• Bayer: collaborator

Related Publications (1)

• Wang Y, Xu F, Song C, Wang X, Zhou H, Qu T, Li H, Luo Q, Lei W, Yin Y, Huang F, Chen M. Cyclic guanosine monophosphate-protein kinase G signaling attenuates aortic valve calcification through ULK1-mediated autophagy. Signal Transduct Target Ther. 2026 Mar 12;11(1):90. doi: 10.1038/s41392-026-02624-5.

  PMID: 41820291 BACKGROUND

MeSH Terms

Conditions

Aortic Valve Disease; Aortic Valve Stenosis

Interventions

vericiguat

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Fangyang Huang, MD

CONTACT

+86-18980607283; fyhuang1989@wchscu.cn

Yan Wang, MD

CONTACT

+86-15319969201; gloriawang_98@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Cardiology

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share