Isolated Surgical Aortic Valve Replacement in Low Risk AS Patients

Not Applicable

Not yet recruiting

• Conditions: Aortic Stenosis

• Registration Number: NCT06924151
• Lead Sponsor: Osaka University

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.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-11
• Study Start: 2025-04
• Study First Submitted QC: 2025-04-04
• Last Update Submitted: 2025-04-04
• Study First Posted: 2025-04-11
• Last Update Posted: 2025-04-11
• Primary Completion: 2027-03
• Study Completion: 2028-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 800

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (40)

Nagoya Tokusyukai General Hospital; 🇯🇵 Kasugai, Aichi, Japan

Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital; 🇯🇵 Nagoya, Aichi, Japan

New Tokyo Hospital; 🇯🇵 Matsudo, Chiba, Japan

Chibanishi General Hospital; 🇯🇵 Matsudo, Chiba, Japan

Tokyo Bay Urayasu Ichikawa Medical Center; 🇯🇵 Urayasu, Chiba, Japan

Kokura Memorial Hospital; 🇯🇵 Kitakyusyu, Fukuoka, Japan

Kurume University; 🇯🇵 Kurume, Fukuoka, Japan

Hyogo Medical University; 🇯🇵 Nishinomiya, Hyogo, Japan

Kawasakisaiwai Hospital; 🇯🇵 Kawasaki, Kanagawa, Japan

Shinshu University; 🇯🇵 Matsumoto, Nagano, Japan

Tokai University; 🇯🇵 Isehara, Kanagawa, Japan

Shonan Kamakura General Hospital; 🇯🇵 Kamakura, Kanagawa, Japan

St.Marianna University School of Medicine; 🇯🇵 Kawasaki, Kanagawa, Japan

Kishiwada Tokusyukai Hospital; 🇯🇵 Kishiwada, Osaka, Japan

Kindai University Hospital; 🇯🇵 Osakasayama, Osaka, Japan

Yuuai Medical Center; 🇯🇵 Tomigusuku, Okinawa, Japan

Osaka Rosai Hospital; 🇯🇵 Sakai, Osaka, Japan

National Cerebral and Cardiovascular Center; 🇯🇵 Suita, Osaka, Japan

Saitama Medical University International Medical Center; 🇯🇵 Hidaka, Saitama, Japan

Dokkyo Medical University Saitama Medical Center; 🇯🇵 Koshigaya, Saitama, Japan

Seirei Hamamatsu General Hospital; 🇯🇵 Hamamatsu, Shizuoka, Japan

Hamamatsu University Shool of Medicine; 🇯🇵 Hamamatsu, Shizuoka, Japan

Dokkyo Medical University; 🇯🇵 Shimotsuga, Tochigi, Japan

Sakakibara Heart Institute; 🇯🇵 Fuchu, Tokyo, Japan

Tokyo Women's Medical University; 🇯🇵 Shinjuku, Tokyo, Japan

Tottori University; 🇯🇵 Yonago, Tottori, Japan

Oita University; 🇯🇵 Oita, Yufu, Japan

Fukui Cardiovascular center; 🇯🇵 Fukui, Japan

Kyushu Univerisity; 🇯🇵 Fukuoka, Japan

Kagoshima Medical Center; 🇯🇵 Kagoshima, Japan

Chikamori Hospital; 🇯🇵 Kochi, Japan

Kumamoto University; 🇯🇵 Kumamoto, Japan

Nagasaki University; 🇯🇵 Nagasaki, Japan

Niigata University Medical and Dental Hospital; 🇯🇵 Niigata, Japan

The Sakakibara Heart Institute of Okayama; 🇯🇵 Okayama, Japan

Osaka International Medical and Science Center; 🇯🇵 Osaka, Japan

Osaka General Medical Center; 🇯🇵 Osaka, Japan

Shizuoka General Hospital; 🇯🇵 Shizuoka, Japan

Tokushima University; 🇯🇵 Tokushima, Japan

Wakayama Medical University; 🇯🇵 Wakayama, Japan