NCT02481258

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2015

Completed
22 days until next milestone

First Submitted

Initial submission to the registry

June 23, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 25, 2015

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2018

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
2 months until next milestone

Results Posted

Study results publicly available

January 18, 2020

Completed
Last Updated

January 22, 2021

Status Verified

January 1, 2021

Enrollment Period

3.1 years

First QC Date

June 23, 2015

Results QC Date

August 6, 2019

Last Update Submit

January 4, 2021

Conditions

Keywords

StenosisAortic ValveAortaCalcifiedCalcificCalcification

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • Change in Levels of Plasma Interleukin-6

    baseline, 6 mos

  • Change in Aortic Valve Function: Aortic Valve Area

    baseline, 6 mos

  • Change in Left Ventricular Function

    baseline, 6 mos

  • Change in Plasma Tumor Necrosis Factor Alpha

    Baseline, 6 months

  • Change in Aortic Valve Function: Transvalvular Pressure Gradient

    baseline, 6 mos

Study Arms (2)

Ataciguat (HMR1766)

EXPERIMENTAL

200mg taken daily for 12 months

Drug: Ataciguat (HMR1766)

Matching Placebo

PLACEBO COMPARATOR

Taken Daily for 12 months

Other: Placebo Comparator: Matching Placebo

Interventions

Ataciguat (HMR1766)

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Aortic Valve StenosisConstriction, PathologicCalcinosis

Interventions

5-chloro-2-(5-chlorothiophene-2-sulfonylamino)-N-(4-(morpholine-4-sulfonyl)phenyl)benzamide

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow ObstructionPathological Conditions, AnatomicalPathological Conditions, Signs and SymptomsCalcium Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Jordan D. Miller, Ph.D.
Organization
Mayo Clinic

Study Officials

  • Jordan D Miller, PhD

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
SAC II

Study Record Dates

First Submitted

June 23, 2015

First Posted

June 25, 2015

Study Start

June 1, 2015

Primary Completion

July 1, 2018

Study Completion

December 1, 2019

Last Updated

January 22, 2021

Results First Posted

January 18, 2020

Record last verified: 2021-01

Locations