Phase 2 N=23 Randomized Double-blind Treatment

A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification

Aortic Valve Stenosis

Bottom Line

View on ClinicalTrials.gov: NCT02481258 ↗

Enrolled (actual)

Serious AEs

8.3%

Results posted

Jan 2020

Primary outcome: Primary: Changes in Aortic Valve Calcium Levels — 65; 215 Arbitrary Units — p=0.05

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Ataciguat (HMR1766) (Drug); Placebo Comparator: Matching Placebo (Other)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: Mayo Clinic
Primary completion: Jul 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Changes in Aortic Valve Calcium Levels	65; 215	0.05
SECONDARY Change in Levels of Plasma Interleukin-6	2.3; -0.2	—
SECONDARY Change in Aortic Valve Function: Aortic Valve Area	-0.07; -0.129	>0.05
SECONDARY Change in Left Ventricular Function	0.6; -2.8	>0.05
SECONDARY Change in Plasma Tumor Necrosis Factor Alpha	1.9; 2.8	—
SECONDARY Change in Aortic Valve Function: Transvalvular Pressure Gradient	1.8; 3.6	—

Summary

The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate calcific aortic valve stenosis. Secondary and tertiary objectives are to determine whether Ataciguat slows progression of aortic valve function, reduces systemic inflammation, and prevents left ventricular dysfunction in patients with moderate calcific aortic valve stenosis.

Eligibility Criteria

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 AU from chest CT
Ejection fraction >50%

Exclusion Criteria

Orthostatic intolerance or symptomatic hypotension prior to study or during study visits
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 NO-sGC-cGMP signaling (sildenafil, nitrates, etc.)
Prescription of Warfarin (Coumadin) for chronic anticoagulation
Concomitant participation in other trials at Mayo Clinic or elsewhere
Use of phenytoin or related compounds for any indication
Chronic midazolam treatment for any indication
Use of monoamine oxidase inhibitors for any indication
Use of anti-diabetic drugs in the sulfonylurea family

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02481258). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.