The purpose of this study is to evaluate if ataciguat slows the progression of moderate calcific aortic valve stenosis in adults.
This study will be conducted in two parts: Part A and Part B. The purpose of Part A is to investigate whether ataciguat slows the progression of aortic valve calcium (AVC) deposition in adults with moderate calcific aortic valve stenosis (CAVS). The safety, tolerability, and pharmacokinetics of ataciguat will also be evaluated. Approximately 132 participants will be enrolled in Part A. Enrollment in Part B will begin once enrollment in Part A is complete. The purpose of Part B is to investigate whether ataciguat slows the rate of aortic valve area (AVA) loss and to evaluate the effect of ataciguat on peak oxygen consumption (VO2) in participants with moderate CAVS. The safety and tolerability of ataciguat will also be evaluated. Approximately 1144 participants will be enrolled in Part B.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,276
(Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24
Time frame: Week 24
(Part B Dual-Primary) Percent change in Aortic Valve Area (AVA) as measured by echocardiogram from baseline to Week 48
Time frame: Week 48
(Part B Dual-Primary) Change in peak VO2 by CPET from baseline to Week 48
Time frame: Week 48
(Part A) Correlation in the change in AVC as assessed by non-contract CT and change in VO2 as assessed be remote cardiac monitoring devices at Week 48
Time frame: Week 48
(Part A) Change in VO2 as assessed by remote cardiac monitoring devices from baseline to Week 48
Time frame: Week 48
(Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48
Time frame: Week 48
(Part A) Change in Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) from baseline to Week 48
KCCQ-23 is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score.
Time frame: Week 48
(Part B) Change in AVC score as assessed by non-contrast CT from baseline to Week 48
Time frame: Week 48
(Part B) Time to decision to proceed with TAVR/SAVR or all-cause death
Time frame: Week 158
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University of Alabama at Birmingham (UAB) - Medical Center
Birmingham, Alabama, United States
RECRUITINGHeart Center Research LLC
Huntsville, Alabama, United States
RECRUITINGOnyx Clinical Research - Peoria
Peoria, Arizona, United States
NOT_YET_RECRUITINGNational Heart Institute
Beverly Hills, California, United States
RECRUITINGHoag Memorial Hospital Presbyterian
Newport Beach, California, United States
RECRUITINGProfound Research LLC at Southern California Heart Specialists
Pasadena, California, United States
RECRUITINGUniversity of California, San Francisco (UCSF) - Medical Center
San Francisco, California, United States
RECRUITINGLundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
Torrance, California, United States
RECRUITINGHCA Florida - JFK Hospital
Atlantis, Florida, United States
RECRUITINGNew Generation of Medical Research
Hialeah, Florida, United States
RECRUITING...and 48 more locations
(Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48
Time frame: Week 48