Vericiguat for the Inhibition of Calcific Aortic Valve Stenosis Progression

ConditionsCalcific Aortic Valve Disease AORTIC VALVE DISEASES Aortic Valve Stenosis

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age35-80

SponsorWest China Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Parallel

Treatments tested in this trial

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
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.

Treatment groups

238 Participants

are divided into 2 treatment groups

Group A: VericiguatActive comparator 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

At 24 months

Secondary outcomes

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).

A three-tier hierarchical composite endpoint, compared using the Win Ratio method, ranked by clinical importance: Tier 1: Time to all-cause death. Tier 2: Time to aortic valve-related clinical events (aortic valve replacement \[TAVR or SAVR\] or first hospitalization for aortic stenosis). Tier 3: Change in aortic valve calcification (AVC) score from baseline at 24 months (log-transformed). A smaller increase (slower calcification progression) is favored.

Time frame

Up to 24 months

Change in Aortic Valve Calcium (AVC) Score at 12 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

Time frame

At 12 months

Change from baseline in aortic valve calcium volume

The change in aortic valve calcium volume (in cubic millimeters) from baseline to 12 and 24 months, measured by non-contrast cardiac CT. Higher scores mean worse outcome

Time frame

At 12 and 24 months

Change in Aortic Valve Peak Velocity

Change in transthoracic echocardiography-measured aortic valve peak velocity from baseline.

Time frame

At 6, 12, 18, and 24 months

Other outcomes

Change in Coronary Artery Calcium Score at 12 and 24 Months

Change in coronary artery calcium score from baseline, measured by non-contrast cardiac CT (Agatston method). Higher scores mean a worse outcome.

Time frame

At 12 and 24 months

Change in Cardiac Magnetic Resonance Parameters at 24 Months

Change in cardiac magnetic resonance (CMR)-measured parameters from baseline, including left ventricular mass index, extracellular volume fraction, and myocardial fibrosis burden (late gadolinium enhancement).

Time frame

At 24 months

Change in Echocardiographic Left Ventricular Mass Index

Change in left ventricular mass index from baseline, measured by transthoracic echocardiography. Left ventricular mass is calculated as: LVM (g) = {0.8 × 1.04 × \[(IVSd + LVIDd + PWd)³ - LVIDd³\] + 0.6} / body surface area (g/m²).

Time frame

At 6, 12, 18, and 24 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

West China Hospital

Lead sponsor

Bayer

Collaborator

Source ClinicalTrials.gov

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