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RecruitingNCT07001800KATALYST-AVUpdated Jul 6, 2026

Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis: A Randomized, Placebo Controlled Study

A Phase 2/3 interventional study of Ataciguat and Placebo in Moderate Aortic Valve Stenosis, sponsored by Kardigan, Inc.. Recruiting at 74 sites in 2 countries. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-07-06.

Sponsored by Kardigan, Inc. · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
1,276
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate if ataciguat slows the progression of moderate calcific aortic valve stenosis in adults.

Read the detailed description

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.

02

Conditions studied

  • Moderate Aortic Valve Stenosis

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Keywords

  • Ataciguat
  • sGC activator
  • sGC stimulator
  • Aortic valve stenosis
  • Moderate aortic valve stenosis
  • Calcific aortic valve stenosis
  • CAVS
  • Moderate Calcific Aortic Valve Stenosis
  • Aortic Stenosis (AS)
03

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  1. Adult male or female at least 50 years of age
  2. Has moderate CAVS as defined by:

    1. An AVA of ≥1.0 cm2 to ≤1.50 cm2
    2. An AVC score between >300 to 1200 Agatston units (AU) for women and between >300 to 2000 AU for men
  3. Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Imaging Core Laboratory
  4. For participants in CPET sub-study in Part A and all participants in Part B: If on beta blockade, the dose must be stable for at least 90 days prior to the Screening Visit with no anticipated changes during the study

Key Exclusion Criteria:

  1. For participants in the CPET sub-study in Part A and all participants in Part B: Has any medical or physical condition that, in the Investigator's opinion, could lead to an inability to complete Protocol-required CPET procedures (eg, pulmonary disease, joint, leg, hip, back conditions that limit physical activity, or other absolute contraindications for CPET)
  2. Anticipated or planned prior aortic valve replacement, repair, surgery, or intervention in the next 6 months
  3. Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation
  4. Has suspected or known congenital aortic valve disease including bicuspid aortic valve
  5. New York Heart Association (NYHA) Class IV heart failure symptoms and/or requires continuous inotropes
  6. Has history of hypertrophic, genetic/familial cardiomyopathy or cardiomyopathy related to amyloid or sarcoid
  7. Has untreated obstructive coronary artery disease or anticipating coronary stenting surgery
  8. Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
1,276 participants (estimated)

Study arms

  • Experimental
    Ataciguat

    Drug: Ataciguat

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugAtaciguat

    Ataciguat will be administrated daily for up to 156 weeks

  • DrugPlacebo

    Placebo will be administrated daily for up to 156 weeks

05

What researchers measure

Primary outcomes

  1. (Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24

    Time frame: Week 24

  2. (Part B Dual-Primary) Percent change in Aortic Valve Area (AVA) as measured by echocardiogram from baseline to Week 48

    Time frame: Week 48

  3. (Part B Dual-Primary) Change in peak VO2 by CPET from baseline to Week 48

    Time frame: Week 48

Secondary outcomes

  1. (Part A) Correlation in the change in AVC as assessed by non-contrast CT and change in VO2 at Week 48

    Time frame: Week 48

  2. (Part A) Change in VO2 from baseline to Week 48

    Time frame: Week 48

  3. Change in left ventricular diastolic function as assessed by E/e' from baseline to Week 48

    Time frame: Week 48

  4. (Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48

    Time frame: Week 48

  5. (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

  6. (Part B) Change in AVC score as assessed by non-contrast CT from baseline to Week 48

    Time frame: Week 48

  7. (Part B) Time to decision to proceed with TAVR/SAVR or all-cause death

    Time frame: Week 158

  8. (Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48

    Time frame: Week 48

06

Study locations

49 of 74 sites recruiting
  • University of Alabama at Birmingham (UAB) - Medical Center
    Birmingham, Alabama 35233, United States
    Recruiting
  • Heart Center Research LLC
    Huntsville, Alabama 35801, United States
    Recruiting
  • Mayo Clinic - Phoenix
    Phoenix, Arizona 85259, United States
    Not yet recruiting
  • National Heart Institute
    Beverly Hills, California 90211, United States
    Recruiting
  • UCLA Ronald Reagan Medical Center
    Los Angeles, California 90095, United States
    Not yet recruiting
  • Hoag Memorial Hospital Presbyterian
    Newport Beach, California 92663, United States
    Recruiting
  • Profound Research LLC at Southern California Heart Specialists
    Pasadena, California 91105, United States
    Recruiting
  • University of California, San Francisco (UCSF) - Medical Center
    San Francisco, California 94143, United States
    Recruiting
  • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
    Torrance, California 90502, United States
    Recruiting
  • HCA Florida - JFK Hospital
    Atlantis, Florida 33462, United States
    Recruiting
  • New Generation of Medical Research
    Hialeah, Florida 33016, United States
    Recruiting
  • Memorial Healthcare System
    Hollywood, Florida 33021, United States
    Not yet recruiting
  • Jacksonville Center for Clinical Research
    Jacksonville, Florida 32216, United States
    Recruiting
  • University of Miami
    Miami, Florida 33136, United States
    Not yet recruiting
  • New Generation of Medical Research - Naples
    Naples, Florida 34116, United States
    Recruiting
  • Flourish Research - St. Augustine
    Saint Augustine, Florida 32086, United States
    Recruiting
  • Sarasota Memorial Hospital
    Sarasota, Florida 34239, United States
    Recruiting
  • University of South Florida
    Tampa, Florida 33606, United States
    Recruiting
  • Wellstar Kennestone Hospital
    Marietta, Georgia 30060, United States
    Not yet recruiting
  • Northwestern University The Feinberg School of Medicine
    Chicago, Illinois 60611, United States
    Recruiting
  • Ascension Heart and Vascular/Alexian Brothers Heart & Vascular Institute
    Elk Grove Village, Illinois 60007, United States
    Recruiting
  • NorthShore University Health System
    Glenview, Illinois 60026, United States
    Recruiting
  • Riverside Medical Center - Illinois
    Kankakee, Illinois 60901, United States
    Not yet recruiting
  • Cardiovascular Medicine
    Moline, Illinois 61265, United States
    Not yet recruiting
  • Midwest Cardiovascular Institute
    Naperville, Illinois 60540, United States
    Recruiting
  • Methodist Medical Center of Illinois
    Peoria, Illinois 61636, United States
    Recruiting
  • Midwest Cardiovascular Research and Education Foundation
    Elkhart, Indiana 46514, United States
    Recruiting
  • The Heart Hospital at Deaconess Gateway
    Newburgh, Indiana 47630, United States
    Not yet recruiting
  • University of Louisville Health
    Louisville, Kentucky 40202, United States
    Recruiting
  • University of Maryland Medical Center
    Baltimore, Maryland 21201, United States
    Recruiting
  • Johns Hopkins University School of Medicine
    Baltimore, Maryland 21287, United States
    Recruiting
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
    Recruiting
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
    Recruiting
  • Corewell Health
    Royal Oak, Michigan 48073, United States
    Recruiting
  • Henry Ford Hospital
    West Bloomfield, Michigan 48322, United States
    Recruiting
  • M Health Fairview St. John's Hospital
    Maplewood, Minnesota 55109, United States
    Not yet recruiting
  • Mayo Clinic - Rochester
    Rochester, Minnesota 55905, United States
    Recruiting
  • Washington University
    St Louis, Missouri 63110, United States
    Recruiting
  • Missouri Baptist Medical Center
    St Louis, Missouri 63131, United States
    Not yet recruiting
  • Deborah Heart and Lung Center
    Browns Mills, New Jersey 08015, United States
    Not yet recruiting
  • Virtua Our Lady of Lourdes Hospital
    Camden, New Jersey 08103, United States
    Not yet recruiting
  • Atlantic Health System - Morristown Medical Center
    Morristown, New Jersey 85831, United States
    Not yet recruiting
  • Inspira Medical Centers
    Mullica Hill, New Jersey 08062, United States
    Not yet recruiting
  • Inspira Medical Center of Vineland
    Vineland, New Jersey 08302, United States
    Not yet recruiting
  • Albany Medical Center
    Albany, New York 12208, United States
    Recruiting
  • University of Buffalo
    Buffalo, New York 14203, United States
    Withdrawn
  • Montefiore Medical Center
    The Bronx, New York 10467, United States
    Recruiting
  • Duke University School of Medicine
    Durham, North Carolina 27710, United States
    Recruiting
  • Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health
    Greensboro, North Carolina 27401, United States
    Recruiting
  • Sanford Fargo
    Fargo, North Dakota 58122, United States
    Recruiting
  • The Lindner Center for Research and Education at The Christ Hospital
    Cincinnati, Ohio 45219, United States
    Recruiting
  • Bethesda North Hospital, TriHealth, Inc
    Cincinnati, Ohio 45242, United States
    Not yet recruiting
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
    Recruiting
  • ProMedica Toledo Hospital
    Toledo, Ohio 43606, United States
    Not yet recruiting
  • Ascension St. John Hospital
    Tulsa, Oklahoma 74104, United States
    Recruiting
  • Providence St. Vincent Medical Center
    Portland, Oregon 97225, United States
    Not yet recruiting
  • Penn Medicine Lancaster General Hospital
    Lancaster, Pennsylvania 17602, United States
    Not yet recruiting
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
    Recruiting
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15213, United States
    Recruiting
  • OnSite Clinical Solutions, LLC - Rock Hill
    Rock Hill, South Carolina 29732, United States
    Recruiting
  • TriStar Centennial Medical Center
    Nashville, Tennessee 37203, United States
    Recruiting
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
    Recruiting
  • St. David's Heart and Vascular dba Austin Heart - Main Office
    Austin, Texas 78705, United States
    Recruiting
  • Methodist Dallas Medical Center
    Dallas, Texas 75203, United States
    Not yet recruiting
  • Houston Methodist Hospital
    Houston, Texas 77030, United States
    Recruiting
  • University of Texas Medical Branch - Galveston
    Houston, Texas 77555, United States
    Not yet recruiting
  • Baylor Scott and White - The Heart Hospital Baylor Plano
    Plano, Texas 75093, United States
    Recruiting
  • Methodist Hospital - San Antonio
    San Antonio, Texas 78229, United States
    Recruiting
  • Houston Methodist Sugar Land Hospital
    Sugar Land, Texas 77479, United States
    Not yet recruiting
  • University of Utah Hospital & Clinics
    Salt Lake City, Utah 84112, United States
    Recruiting
  • St. Boniface Hospital
    Winnipeg, Mantioba R2H 2A6, Canada
    Not yet recruiting
  • Montreal Heart Institute - Institut de Cardiologie de Montreal
    Montreal, Quebec H1T 1C8, Canada
    Recruiting
  • Centre Hospitalier de l Universite de Montreal (CHUM)
    Montreal, Quebec H2X 0C1, Canada
    Not yet recruiting
  • Institut Universitaire de Cardiologie et de Pneumologie De Quebec
    Québec, Quebec GIV 4G5, Canada
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07001800
Lead sponsor
Kardigan, Inc.
Responsible party
Sponsor
First posted
Jun 3, 2025
Start date
Jun 27, 2025
Primary completion
Aug 31, 2028 (estimated)
Completion
Sep 30, 2030 (estimated)
Last update
Jul 6, 2026

Study contacts

Kardigan Clinical Trial Information Team
Contact
clinicaltrials@kardigan.bio
1-877-310-5135

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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