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

Overview

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.

Interventions

• Procedure surgical aortic valve replacement
  SAVR
• Procedure Transcatheter aortic valve replacement
  TAVR

Primary outcome measures

• 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]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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%

• 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.
• 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:

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 37 centers

• Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital — Nagoya
• New Tokyo Hospital — Matsudo
• Chibanishi General Hospital — Matsudo
• Tokyo Bay Urayasu Ichikawa Medical Center — Urayasu
• Fukui Cardiovascular center — Fukui-shi
• Kyushu Univerisity — Fukuoka
• Kokura Memorial Hospital — Kitakyushu
• Kurume University — Kurume
• … and 29 more centers

Identifiers

NCT: NCT06924151 · AMETHYST-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗