Aortic Valve StenosisPhase 2CAVSNCT02481258
A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification
A Phase 2 study testing Ataciguat (HMR1766) in people with Aortic Valve Stenosis, run by Mayo Clinic at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- Ataciguat (HMR1766)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to 1 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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
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.
Read the detailed 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.
- Conditions
- Aortic Valve Stenosis
- Being tested
- Ataciguat (HMR1766), Placebo Comparator: Matching Placebo
- Keywords
- Stenosis, Aortic Valve, Aorta, Calcified, Calcific, Calcification
- Medical subject headings
- Aortic Valve Stenosis, Constriction, Pathologic, Calcinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ataciguat (HMR1766)Drug
Placebo Comparator: Matching PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Ataciguat (HMR1766) | Experimental | 200mg taken daily for 12 months Receives: Drug: Ataciguat (HMR1766) |
| Matching Placebo | Placebo comparator | Taken Daily for 12 months Receives: Other: Placebo Comparator: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: baseline, 6 mos
Secondary outcomes (5)
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.
Measured: baseline, 6 mos
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.
Measured: baseline, 6 mos
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).
Measured: baseline, 6 mos
Change in Plasma Tumor Necrosis Factor Alpha
Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines.
Measured: Baseline, 6 months
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.
Measured: baseline, 6 mos
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion1 Jul 2018
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Jordan D. Miller, Ph.D., Mayo Clinic
- Investigators
- Jordan D Miller, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02481258
- Sponsor's protocol ID
- 14-006469
- Other IDs
- TR 000954
- Acronym
- CAVS
- Status last verified
- Jan 2021
- First submitted
- 23 Jun 2015
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zhang B, Enriquez-Sarano M, Schaff HV, Michelena HI, Roos CM, Hagler MA, Zhang H, Casaclang-Verzosa G, Huang R, Bartoo A, Ranadive S, Joyner MJ, Pislaru S, Nkomo VT, Kremers WK, Araoz PA, Singh G, Walters MA, Hawkinson J, Cunningham KY, Sung J, Dunagan B, Ye Z, Miller JD. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy. Circulation. 2025 Apr;151(13):913-930. doi: 10.1161/CIRCULATIONAHA.123.066523. Epub 2025 Feb 24.
PubMed 39989354
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02481258
- Acronym / sponsor ID
- CAVS / 14-006469
- Conditions
- Aortic Valve Stenosis
- Keywords
- Stenosis, Aortic Valve, Aorta, Calcified, Calcific, Calcification
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Sanofi, National Institutes of Health (NIH)
- Study start
- Jun 2015
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 25 Jun 2015 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ataciguat (HMR1766) | Experimental | Drug: Ataciguat (HMR1766)200mg taken daily for 12 months |
| Matching Placebo | Placebo comparator | Other: Placebo Comparator: Matching PlaceboTaken Daily for 12 months |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ataciguat (HMR1766) | Drug | Ataciguat (HMR1766) |
| Placebo Comparator: Matching Placebo | Other | Matching Placebo |
Primary outcome
Changes in Aortic Valve Calcium Levels
Time frame: baseline, 6 mos
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).
5 secondary outcomes
Change in Levels of Plasma Interleukin-6
Time frame: baseline, 6 mos
Change in Aortic Valve Function: Aortic Valve Area
Time frame: baseline, 6 mos
Change in Left Ventricular Function
Time frame: baseline, 6 mos
Change in Plasma Tumor Necrosis Factor Alpha
Time frame: Baseline, 6 months
Change in Aortic Valve Function: Transvalvular Pressure Gradient
Time frame: baseline, 6 mos
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39989354Zhang B, Enriquez-Sarano M, Schaff HV, Michelena HI, Roos CM, Hagler MA, Zhang H, Casaclang-Verzosa G, Huang R, Bartoo A, Ranadive S, Joyner MJ, Pislaru S, Nkomo VT, Kremers WK, Araoz PA, Singh G, Walters MA, Hawkinson J, Cunningham KY, Sung J, Dunagan B, Ye Z, Miller JD. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy. Circulation. 2025 Apr;151(13):913-930. doi: 10.1161/CIRCULATIONAHA.123.066523. Epub 2025 Feb 24.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordan D Miller, PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ataciguat (HMR1766) in people with Aortic Valve Stenosis, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Aortic Valve Calcium Levels (time frame: baseline, 6 mos). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02481258, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.