Clinical trial NCT06924151: Isolated Surgical Aortic Valve Replacement in Low Risk AS Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: Osaka University
Sponsor class: OTHER
First posted: 2025-04-11
Enrollment: 800
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite endpoint of all-cause mortality, all stroke, and rehospitalization (valve-related or procedure-related and including heart failure)
timeFrame: at 1 year post procedure
Secondary outcomes:
measure: the rate of all-cause mortality or disabling stroke
timeFrame: at one year
measure: the rate of all-cause mortality
timeFrame: at one year
measure: the rate of all stroke
timeFrame: at one year
measure: the rate of disabling stroke
timeFrame: at one year
measure: the rate of rehospitalization (valve-related or procedure-related and including heart failure)
timeFrame: at one year
measure: the rate of new bundle branch block or new pacemaker implantation
timeFrame: at one year
measure: the rate of new onset of atrial fibrillation
timeFrame: at 30 days
measure: the rate of life-threatening bleeding
timeFrame: at one year
measure: the rate of occurrence of perivalvular regurgitation ≥ mild by echocardiography
timeFrame: at one year
measure: Quality of life as assessed by KCCQ
timeFrame: at one year
measure: Quality of life as assessed by EQ-5D-5L
timeFrame: at one year
measure: the rate of prosthetic valve endocarditis
timeFrame: at one year
measure: the rate of prosthetic valve thrombosis
timeFrame: at one year
measure: the rate of valve-related dysfunction requiring repeat procedure
timeFrame: at one year
Other outcomes:
measure: All cause mortality
timeFrame: at 30 days
measure: The rate of all stroke (disabling and nondisabling)
timeFrame: at 30 days
measure: The rate of Rehospitalization (valve-related or procedure-related and including heart failure)
timeFrame: at 30 days
measure: All cause mortality or all stroke
timeFrame: at one year
measure: All cause mortality or disabling stroke
timeFrame: at 30 days
measure: The rate of vascular complications (major)
timeFrame: at 30 days and one year
measure: The rate of Bleeding complications (life threatening, disabling or major)
timeFrame: at 30 days
measure: The rate of myocardial infarction
timeFrame: at 30 days and one year
measure: The rate of acute kidney injury
timeFrame: at 30 days
measure: the rate of new bundle branch block or new pacemaker implantation
timeFrame: at 30 days
measure: the rate of occurrence of perivalvular regurgitation ≥ mild by echocardiography
timeFrame: at 30 days
measure: The rate of coronary obstruction requiring intervention
timeFrame: at 30 days and one year
measure: New York Heart Association class
timeFrame: at 30 days and one year
measure: Six-minute walk test
timeFrame: at 30 days and one year
measure: The length of postoperative ICU stay
timeFrame: up to one year
measure: Discharge location
timeFrame: up to one year
measure: Health status as evaluated by Quality of Life questionnaires (KCCQ)
timeFrame: at 30 days
measure: Health status as evaluated by Quality of Life questionnaires (EQ-5D-5L)
timeFrame: at 30 days
measure: Cognitive function assessed by the MMSE
timeFrame: at one year
measure: The rate of new onset atrial fibrillation
timeFrame: at one year
measure: Endpoints of minimally invasive aortic valve replacement (MICS AVR) vs TAVR
timeFrame: at 30 days and one year
Locations:
city: Kasugai
country: Japan
facility: Nagoya Tokusyukai General Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
state: Aichi
city: Matsudo
country: Japan
facility: New Tokyo Hospital
state: Chiba
city: Matsudo
country: Japan
facility: Chibanishi General Hospital
state: Chiba
city: Urayasu
country: Japan
facility: Tokyo Bay Urayasu Ichikawa Medical Center
state: Chiba
city: Kitakyusyu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University
state: Fukuoka
city: Nishinomiya
country: Japan
facility: Hyogo Medical University
state: Hyogo
city: Isehara
country: Japan
facility: Tokai University
state: Kanagawa
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: Kawasakisaiwai Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: St.Marianna University School of Medicine
state: Kanagawa
city: Matsumoto
country: Japan
facility: Shinshu University
state: Nagano
city: Tomigusuku
country: Japan
facility: Yuuai Medical Center
state: Okinawa
city: Kishiwada
country: Japan
facility: Kishiwada Tokusyukai Hospital
state: Osaka
city: Osakasayama
country: Japan
facility: Kinki University Hospital
state: Osaka
city: Sakai
country: Japan
facility: Osaka Rosai Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Hamamatsu
country: Japan
facility: Seirei Hamamatsu General Hospital
state: Shizuoka
city: Hamamatsu
country: Japan
facility: Hamamatsu University Shool of Medicine
state: Shizuoka
city: Shimotsuga
country: Japan
facility: Dokkyo Medical University
state: Tochigi
city: Fuchu
country: Japan
facility: Sakakibara Heart Institute
state: Tokyo
city: Shinjuku
country: Japan
facility: Tokyo Women's Medical University
state: Tokyo
city: Yonago
country: Japan
facility: Tottori University
state: Tottori
city: Oita
country: Japan
facility: Oita University
state: Yufu
city: Fukui
country: Japan
facility: Fukui Cardiovascular center
city: Fukuoka
country: Japan
facility: Kyushu Univerisity
city: Kagoshima
country: Japan
facility: Kagoshima Medical Center
city: Kochi
country: Japan
facility: Chikamori Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University
city: Nagasaki
country: Japan
facility: Nagasaki University
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Okayama
country: Japan
facility: The Sakakibara Heart Institute of Okayama
city: Osaka
country: Japan
facility: Osaka International Medical and Science Center
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka General Hospital
city: Tokushima
country: Japan
facility: Tokushima University
city: Wakayama
country: Japan
facility: Wakayama Medical University
Study officials:
References: