Vericiguat for the Inhibition of Calcific Aortic Valve Stenosis Progression
Trial statusNot yet recruiting
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
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
Treatments tested in this trial
- Vericiguat (BAY1021189)
- Placebo
Treatment groups
238 Participants
are divided into 2 treatment groupsLocations
Sponsors and collaborators
West China Hospital
Lead sponsor
Bayer
Collaborator
Source ClinicalTrials.gov