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

Mayo Clinic

Status and phase: Completed; Phase 2

Conditions: Aortic Valve Stenosis

Treatments: Drug: Ataciguat (HMR1766); Other: Placebo Comparator: Matching Placebo

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02481258

TR 000954 (Other Identifier)

14-006469

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 α-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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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35 participants in 2 patient groups, including a placebo group

Ataciguat (HMR1766)

Experimental group

Description:

200mg taken daily for 12 months

Treatment:

Drug: Ataciguat (HMR1766)

Matching Placebo

Placebo Comparator group

Description:

Taken Daily for 12 months

Treatment:

Other: Placebo Comparator: Matching Placebo