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

Aortic Valve Stenosis Clinical Trial

— CAVS  

Official title:

A Phase II Randomized, Placebo-Controlled, Double-Blinded Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification in Patients With Moderate Calcific Aortic Valve Stenosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02481258
• Other study ID #: 14-006469
• Secondary ID: TR 000954
• Status: Completed
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: December 1, 2019

Study information

• Verified date: January 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Patients with Moderate Calcific Aortic Valve Stenosis may be eligible for enrollment in this study. Participation lasts 12 months, which includes a total of 3 study visits (baseline/screening visit, 6 month follow up visit and 12 month follow up visit). During each visit, a blood sample will be taken along with other research related tests (Orthostatic Tolerance Standing Test, CT Scan, Echocardiogram, DEXA Scan). Qualifying Participants will be supplied with 6 months worth of study medication or placebo during visits 1 (baseline/screening visit) and 2 (6 month follow up visit) in which they will take at home daily with food. On visit 3 (12 month follow up visit), any remaining study medication or placebo will be returned to study staff.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 1, 2019
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria

1. Age > 50 years

2. Male or female sex

3. Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2

4. Aortic valve calcium levels greater than 300 AU from chest CT

5. Ejection fraction >50%

Exclusion Criteria

1. Orthostatic intolerance or symptomatic hypotension prior to study or during study visits

2. Positive pregnancy test during screening visit

3. Nitrate use or a-antagonist medication use within 24 hours

4. Systolic blood pressure <110 mm Hg

5. Mean systemic arterial pressure <75 mm Hg

6. Severe mitral or aortic regurgitation

7. Retinal or optic nerve problems

8. Recent (=30 days) acute coronary syndrome

9. Oxygen saturation <90% on room air

10. Congenital valve disease

11. Hepatic dysfunction/elevated liver enzymes

12. Prescription of drugs known to alter NO-sGC-cGMP signaling (sildenafil, nitrates, etc.)

13. Prescription of Warfarin (Coumadin) for chronic anticoagulation

14. Concomitant participation in other trials at Mayo Clinic or elsewhere

15. Use of phenytoin or related compounds for any indication

16. Chronic midazolam treatment for any indication

17. Use of monoamine oxidase inhibitors for any indication

18. Use of anti-diabetic drugs in the sulfonylurea family

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Calcinosis
• Constriction, Pathologic

Intervention

Drug:
• Ataciguat (HMR1766)

Other:
• Placebo Comparator: Matching Placebo

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Institutes of Health (NIH), Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Aortic Valve Calcium Levels	This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU).	baseline, 6 mos
Secondary	Change in Levels of Plasma Interleukin-6	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules.	baseline, 6 mos
Secondary	Change in Aortic Valve Function: Aortic Valve Area	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and; mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.	baseline, 6 mos
Secondary	Change in Left Ventricular Function	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements).	baseline, 6 mos
Secondary	Change in Plasma Tumor Necrosis Factor Alpha	Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines.	Baseline, 6 months
Secondary	Change in Aortic Valve Function: Transvalvular Pressure Gradient	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and; mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.	baseline, 6 mos

External Links

•   Mayo Clinic Clinical Trials