Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis

This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis. The primary focus of these studies will be on changes in blood pressure and orthostatic tolerance (i.e., ability to stand up without passing out), and determining whether treatment with Ataciguat results in significant reductions in blood pressure in this patient population.

Inclusion Criteria:

• Age > 50 years
• Male or female sex
• Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2
• Aortic valve calcium levels greater than 300 arbitrary units from chest CT
• Ejection fraction >50%

Exclusion Criteria:

• History of orthostatic intolerance or symptomatic hypotension
• Positive pregnancy test during screening visit
• Nitrate use or α-antagonist medication use within 24 hours
• Systolic blood pressure <110 mm Hg
• Mean systemic arterial pressure <75 mm Hg
• Severe mitral or aortic regurgitation
• Retinal or optic nerve problems
• Recent (≤30 days) acute coronary syndrome
• Oxygen saturation <90% on room air
• Congenital valve disease
• Hepatic dysfunction/elevated liver enzymes
• Prescription of drugs known to alter nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling (sildenafil, nitrates, etc.)
• History of orthostatic intolerance
• Concomitant participation in other trials at Mayo Clinic or elsewhere.