Isolated Surgical Aortic Valve Replacement in Low Risk AS Patients (AMETHYST)

August 21, 2025 updated by: Osaka University

the Prospective, Randomized, Controlled, Multi-center Study to Establish the Safety and Effectiveness of Isolated Surgical Aortic Valve Replacement in Low Risk Patients Who Have Symptomatic Severe Aortic Stenosis

To establish the safety and effectiveness of surgical aortic valve replacement (SAVR) in patients with isolated severe, calcific aortic stenosis who are at low surgical risk.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is the Prospective, Randomized, Controlled, Multi-center Study of Isolated SAVR in Low Risk AS Patients (The AMETHYST trial). Patients will be randomized 1:1 to receive either SAVR or transcatheter heart valve replacement (TAVR) with a commercially available surgical and transcatheter bioprosthetic valves. The aim of this study was to assess the non-inferiority of SAVR compared with TAVR for the combined endpoints of death from any cause, stroke and rehospitalization (hospitalization related to biological valves or procedures or heart failure) at 1 year postoperatively. Patients will be seen for follow-up visits at discharge, 30 days, and annually through 10 years.

Study Type

Interventional

Enrollment (Estimated)

800

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Shigeru Miyagawa, M.D.

Study Contact Backup

Study Locations

  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 4538511
        • Not yet recruiting
        • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
        • Contact:
        • Principal Investigator:
          • Masayoshi Tokoro, M.D.
        • Sub-Investigator:
          • Toshiaki Ito, M.D.
    • Chiba
      • Matsudo, Chiba, Japan, 2402232
      • Matsudo, Chiba, Japan, 2702251
        • Recruiting
        • Chibanishi General Hospital
        • Contact:
        • Principal Investigator:
          • Yoshitsugu Nakamura, M.D.
        • Sub-Investigator:
          • Taisuke Nakayama, M.D.
      • Urayasu, Chiba, Japan, 2790001
        • Recruiting
        • Tokyo Bay Urayasu Ichikawa Medical Center
        • Contact:
        • Principal Investigator:
          • Joji Ito, M.D.
    • Fukui
      • Fukui-shi, Fukui, Japan, 910-0833
        • Not yet recruiting
        • Fukui Cardiovascular center
        • Contact:
        • Principal Investigator:
          • Osamu Monta, M.D.
    • Fukuoka
      • Fukuoka, Fukuoka, Japan, 8128582
        • Recruiting
        • Kyushu Univerisity
        • Contact:
        • Principal Investigator:
          • Akira Shiose, M.D.
        • Sub-Investigator:
          • Hiromichi Sonoda, M.D.
      • Kitakyushu, Fukuoka, Japan, 802-8555
        • Recruiting
        • Kokura Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Shinichi Shirai, M.D.
        • Sub-Investigator:
          • Nobuhisa Ono, M.D.
      • Kurume, Fukuoka, Japan, 8300011
        • Recruiting
        • Kurume University
        • Contact:
        • Principal Investigator:
          • Tohru Takaseya, M.D.
        • Sub-Investigator:
          • Eiki Tayama, M.D.
    • Hyōgo
      • Nishinomiya, Hyōgo, Japan, 6638501
        • Recruiting
        • Hyogo Medical University
        • Contact:
        • Principal Investigator:
          • Kenichi Watanabe, M.D.
        • Sub-Investigator:
          • Taichi Sakaguchi, M.D.
    • Kagoshima-ken
      • Kagoshima, Kagoshima-ken, Japan, 8920853
        • Not yet recruiting
        • Kagoshima Medical Center
        • Contact:
        • Principal Investigator:
          • Naoki Tateishi, M.D.
    • Kanagawa
      • Isehara, Kanagawa, Japan, 2591193
        • Recruiting
        • Tokai University
        • Contact:
        • Principal Investigator:
          • Yohei Ohno, M.D.
        • Sub-Investigator:
          • Yasunori Cho, M.D.
      • Kamakura, Kanagawa, Japan, 2478533
        • Recruiting
        • Shonan Kamakura General Hospital
        • Contact:
        • Principal Investigator:
          • Shigeru Saito, M.D.
        • Sub-Investigator:
          • Tohru Asai, M.D.
      • Kawasaki, Kanagawa, Japan, 2168511
        • Recruiting
        • St.Marianna University School of Medicine
        • Contact:
        • Principal Investigator:
          • Kan Nawata, M.D.
        • Sub-Investigator:
          • Masaki Izumo, M.D.
      • Kawasaki, Kanagawa, Japan, 2120014
        • Recruiting
        • Kawasakisaiwai Hospital
        • Contact:
        • Principal Investigator:
          • Shuichiro Takanashi, M.D.
        • Sub-Investigator:
          • Takayuki Kawamura, M.D.
    • Kochi
      • Kochi, Kochi, Japan, 7808522
        • Recruiting
        • Chikamori Hospital
        • Contact:
        • Principal Investigator:
          • Hiroyuki Irie, M.D.
        • Sub-Investigator:
          • Kazuya Kawai, M.D.
    • Kumamoto
      • Kumamoto, Kumamoto, Japan, 8608556
        • Recruiting
        • Kumamoto University
        • Contact:
        • Principal Investigator:
          • Kenichi Tsujita, M.D.
        • Sub-Investigator:
          • Toshihiro Fukui, M.D.
    • Nagano
      • Matsumoto, Nagano, Japan, 3908621
        • Recruiting
        • Shinshu University
        • Contact:
        • Principal Investigator:
          • Tatsuichiro Seto, M.D.
        • Sub-Investigator:
          • Haruki Tanaka, M.D.
    • Nagasaki
      • Nagasaki, Nagasaki, Japan, 8528501
        • Recruiting
        • Nagasaki University
        • Contact:
        • Principal Investigator:
          • Takashi Miura, M.D.
        • Sub-Investigator:
          • Koji Maemura, M.D.
    • Niigata
      • Niigata, Niigata, Japan, 951-8520
        • Recruiting
        • Niigata University Medical And Dental Hospital
        • Contact:
        • Principal Investigator:
          • Keitaro Domae, M.D.
    • Okayama-ken
      • Okayama, Okayama-ken, Japan, 7000804
        • Recruiting
        • The Sakakibara Heart Institute of Okayama
        • Contact:
        • Principal Investigator:
          • Arudo Hiraoka, M.D.
        • Sub-Investigator:
          • Hidenori Yoshitaka, M.D.
    • Okinawa
      • Tomigusuku, Okinawa, Japan, 9010224
        • Recruiting
        • YUUAI Medical Center
        • Contact:
        • Principal Investigator:
          • Akihiko Yamauchi, M.D.
    • Osaka
      • Kishiwada, Osaka, Japan, 5960042
        • Recruiting
        • Kishiwada Tokusyukai Hospital
        • Contact:
        • Principal Investigator:
          • Satoshi Kuroyanagi, M.D.
      • Osaka, Osaka, Japan, 5438922
        • Recruiting
        • Osaka International Medical and Science Center
        • Contact:
        • Principal Investigator:
          • Yoshiki Sawa, M.D.
        • Sub-Investigator:
          • Yasuhiro Ichibori, M.D.
      • Osaka, Osaka, Japan, 558-8558
        • Recruiting
        • Osaka General Medical Center
        • Contact:
        • Principal Investigator:
          • Naosumi Sekiya, M.D.
        • Sub-Investigator:
          • Atsushi Kikuchi, M.D.
      • Sakai, Osaka, Japan, 591-8025
        • Recruiting
        • Osaka Rosai Hospital
        • Contact:
        • Principal Investigator:
          • Haruhiko Kondoh, M.D.
      • Sayama, Osaka, Japan, 589-8511
        • Recruiting
        • Kinki University Hospital
        • Contact:
        • Principal Investigator:
          • Gaku Nakazawa, M.D.
        • Sub-Investigator:
          • Genichi Sakaguchi, M.D.
    • Saitama
      • Hidaka, Saitama, Japan, 3501298
        • Recruiting
        • Saitama Medical University International Medical Center
        • Contact:
        • Principal Investigator:
          • Akihiro Yoshitake, M.D.
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan, 4308558
        • Recruiting
        • Seirei Hamamatsu General Hospital
        • Contact:
        • Principal Investigator:
          • Masaaki Koide, M.D.
      • Hamamatsu, Shizuoka, Japan, 4313192
        • Recruiting
        • Hamamatsu University Shool of Medicine
        • Contact:
        • Principal Investigator:
          • Kazuma Okamoto, M.D.
        • Sub-Investigator:
          • Yuishiro Maekawa, M.D.
      • Shizuoka, Shizuoka, Japan, 4208527
        • Recruiting
        • Shizuoka General Hospital
        • Contact:
        • Principal Investigator:
          • Hiroshi Tsuneyoshi, M.D.
    • Tochigi
      • Shimotsuga, Tochigi, Japan, 3210293
        • Recruiting
        • Dokkyo Medical University
        • Contact:
        • Principal Investigator:
          • Hirotsugu Fukuda, M.D.
    • Tokushima
      • Tokushima, Tokushima, Japan, 7708503
        • Recruiting
        • Tokushima University
        • Contact:
        • Principal Investigator:
          • Hiroki Hata, M.D.
    • Tokyo
      • Fuchū, Tokyo, Japan, 1830003
        • Recruiting
        • Sakakibara Heart Institute
        • Contact:
        • Principal Investigator:
          • Tomohiro Iwakura, M.D.
        • Sub-Investigator:
          • Itaru Takamisawa, M.D.
      • Shinjuku, Tokyo, Japan, 1628666
        • Recruiting
        • Tokyo Women's Medical University
        • Contact:
        • Principal Investigator:
          • Hiroshi Niinami, M.D.
        • Sub-Investigator:
          • Satoru Domoto, M.D.
    • Tottori
      • Yonago, Tottori, Japan, 6838504
        • Recruiting
        • Tottori University
        • Contact:
        • Principal Investigator:
          • Yasushi Yoshikawa, M.D.
        • Sub-Investigator:
          • Takeshi Onohara, M.D.
    • Wakayama
      • Wakayama, Wakayama, Japan, 6418509
        • Recruiting
        • Wakayama Medical University
        • Contact:
        • Principal Investigator:
          • Kentaro Honda, M.D.
        • Sub-Investigator:
          • Teruaki Wada, M.D.
    • Yufu
      • Ōita, Yufu, Japan, 879-5593
        • Recruiting
        • Oita University
        • Contact:
        • Principal Investigator:
          • Takashi Syuto, M.D.
        • Sub-Investigator:
          • Shinji Miyamoto, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. All study participants must meet the following inclusion criteria 1. Severe, calcific aortic stenosis with the following criteria:

    • Jet velocity ≥4.0 m/s or mean gradient ≥ 40 mmHg OR
    • AVA ≤1.0 cm2 or AVA index ≤ 0.6 cm2/m2 Note: Qualifying TTE must be within 90 days prior to randomization

    AND 2. NYHA class ≥ II OR Exercisee test that demonstrates a limited exercise capacity, abnormal blood pressure response, or arrhythmia OR Asymptomatic patients with LVEF <50%

  2. The Heart Team agrees that the surgical mortality risk is less than 4% according to STS-PROM. The Heart Team's assessment should include evaluation of overall clinical status and comorbidities that may not be adequately captured by risk calculators such as STS-PROM, in addition to the risk score itself.
  3. The patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by certified review board.

Exclusion Criteria:

Candidates will be excluded from the study if any of the following conditions are present:

  1. History of cardiovascular surgery or thoracotomy
  2. Pre-existing other valvular disease, coronary artery disease or aortic disease required intervention Note: interventions for arrhythmia or root enlargement are not considered exclusionary.
  3. Heart Team assessment that chest abnormalities or significant frailty would prevent safe SAVR.
  4. Native aortic annulus size unsuitable for sizes the currently approved and marketed SAVR or TAVR based on preoperative 3D-CT image analysis.
  5. Iliofemoral vessel characteristics that whould preclude safe insertion of the introducer sheath.
  6. Evidence of an acute myocardial infarction or PCI ≤ 30 days before randomization
  7. Aortic valve is unicuspid
  8. Severe aortic regurgitation (>3+)
  9. Severe mitral regurgitation (>3+) or ≥ moderate stenosis
  10. Severe tricuspid regurgitation (>3+) or ≥ moderate stenosis
  11. Pre-existing mechanical or bioprosthetic valve in any position.

  12. Complex coronary artery disease:

    1. Heart Team assessment that CABG is recommended at the time of SAVR
    2. Heart Team assessment that optimal revascularization cannot be performed
  13. Symptomatic carotid or vertebral artery disease or treatment of carotid stenosis within 30 days of randomization
  14. Leukopenia (WBC < 3000 cell/mL), Thrombocytopenia (Plt < 50,000 cell/mL), history of bleeding diathesis or coagulopathy.
  15. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
  16. Hypertrophic cardiomyopathy with obstruction (HOCM)
  17. Ventricular dysfunction with LVEF < 30%
  18. Cardiac imaging (echo, CT, and/or MRI) evidence of intracardiac mass, thrombus or vegetation
  19. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure
  20. Stroke or transient ischemic attack (TIA) within 90 days of randomization
  21. Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy
  22. Active bacterial endocarditis within 180 days of randomization
  23. Severe lung disease (FEV1 < 50% predicted) or currently on home oxygen
  24. Severe pulmonary hypertension (e.g., PA systolic pressure ≥ 2/3 systemic pressure)
  25. History of cirrhosis or active liver disease
  26. Significant abdominal or thoracic aortic disease (such as porcelain aorta, aneurysm, severe calcification, aortic coarctation, etc.) that would preclude cannulation and aortotomy for SAVR or safe passage of the delivery system for TAVR.
  27. Patient refuses blood products.
  28. BMI > 50 kg/m2
  29. Estimated life expectancy < 24 months.
  30. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication.
  31. Immobility or significant cognitive impairment that would prevent completion of study procedure.
  32. Currently participating in an investigational drug or another device study.
  33. Unsuitable as candidates by the principal investigator or a research associate for other reasons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Surgical aortic valve replacement
Surgical aortic valve replacement (SAVR) with free choice of surgical bioprosthesis and free choice of surgical access according to the surgeon's preference
Procedure: surgical aortic valve replacement
SAVR
Active Comparator: Transcatheter aortic valve replacement
Transcatheter aortic valve replacement (TAVR) using the device available in Japan in facilities approved to perform TAVR.
Procedure: Transcatheter aortic valve replacement
TAVR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite endpoint of all-cause mortality, all stroke, and rehospitalization (valve-related or procedure-related and including heart failure)
Time Frame: at 1 year post procedure
at 1 year post procedure

Secondary Outcome Measures

Outcome Measure
Time Frame
the rate of all-cause mortality or disabling stroke
Time Frame: at one year
at one year
the rate of all-cause mortality
Time Frame: at one year
at one year
the rate of all stroke
Time Frame: at one year
at one year
the rate of disabling stroke
Time Frame: at one year
at one year
the rate of rehospitalization (valve-related or procedure-related and including heart failure)
Time Frame: at one year
at one year
the rate of new bundle branch block or new pacemaker implantation
Time Frame: at one year
at one year
the rate of new onset of atrial fibrillation
Time Frame: at 30 days
at 30 days
the rate of life-threatening bleeding
Time Frame: at one year
at one year
the rate of occurrence of perivalvular regurgitation ≥ mild by echocardiography
Time Frame: at one year
at one year
Quality of life as assessed by KCCQ
Time Frame: at one year
at one year
Quality of life as assessed by EQ-5D-5L
Time Frame: at one year
at one year
the rate of prosthetic valve endocarditis
Time Frame: at one year
at one year
the rate of prosthetic valve thrombosis
Time Frame: at one year
at one year
the rate of valve-related dysfunction requiring repeat procedure
Time Frame: at one year
at one year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
All cause mortality
Time Frame: at 30 days
at 30 days
The rate of all stroke (disabling and nondisabling)
Time Frame: at 30 days
at 30 days
The rate of Rehospitalization (valve-related or procedure-related and including heart failure)
Time Frame: at 30 days
at 30 days
All cause mortality or all stroke
Time Frame: at one year
at one year
All cause mortality or disabling stroke
Time Frame: at 30 days
at 30 days
The rate of vascular complications (major)
Time Frame: at 30 days and one year
at 30 days and one year
The rate of Bleeding complications (life threatening, disabling or major)
Time Frame: at 30 days
at 30 days
The rate of myocardial infarction
Time Frame: at 30 days and one year
at 30 days and one year
The rate of acute kidney injury
Time Frame: at 30 days
at 30 days
the rate of new bundle branch block or new pacemaker implantation
Time Frame: at 30 days
at 30 days
the rate of occurrence of perivalvular regurgitation ≥ mild by echocardiography
Time Frame: at 30 days
at 30 days
The rate of coronary obstruction requiring intervention
Time Frame: at 30 days and one year
at 30 days and one year
New York Heart Association class
Time Frame: at 30 days and one year

NYHA Classification criteria:

Class I: Subjects with cardiac disease but without resulting limitations of physical activity Class II: Subjects with cardiac disease resulting in slight limitation of physical activity Class III: Subjects with cardiac disease resulting in marked limitation of physical activity Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort
at 30 days and one year
Six-minute walk test
Time Frame: at 30 days and one year
at 30 days and one year
The length of postoperative ICU stay
Time Frame: up to one year
up to one year
Discharge location
Time Frame: up to one year
  • Home [including return to pre-admission facilities (excluding hospitals)]
  • Other hospital [excluding rehabilitation hospital]
  • Rehabilitation hospital
  • Death
  • Other
up to one year
Health status as evaluated by Quality of Life questionnaires (KCCQ)
Time Frame: at 30 days

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.

This instrument was developed and validated by John Spertus. John is Director of Cardiovascular Education and Outcomes Research at the Mid America Heart Institute, and he is also a Professor of Medicine at the University of Missouri - Kansas City.

In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. For brevity, only the performance characteristics of the overall summary score are presented in this discussion.
at 30 days
Health status as evaluated by Quality of Life questionnaires (EQ-5D-5L)
Time Frame: at 30 days
EQ-5D-5L: Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state
at 30 days
Cognitive function assessed by the MMSE
Time Frame: at one year

It is an 11-question measure that tests five areas of cognitive function:

orientation, registration, attention and calculation, recall, and language. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment.
at one year
The rate of new onset atrial fibrillation
Time Frame: at one year
at one year
Endpoints of minimally invasive aortic valve replacement (MICS AVR) vs TAVR
Time Frame: at 30 days and one year
at 30 days and one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Osaka University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2025

Primary Completion (Estimated)

May 31, 2028

Study Completion (Estimated)

May 31, 2037

Study Registration Dates

First Submitted

February 11, 2025

First Submitted That Met QC Criteria

April 4, 2025

First Posted (Actual)

April 11, 2025

Study Record Updates

Last Update Posted (Estimated)

August 28, 2025

Last Update Submitted That Met QC Criteria

August 21, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMETHYST-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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