PRECISE-AFMR I: A Prospective Randomized Controlled Trial of Transcatheter Mitral Valve Edge-to-Edge Repair in Patients With Atrial Functional Mitral Regurgitation at High Surgical Risk
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 182
- 试验地点
- 1
- 主要终点
- Composite endpoint of all-cause mortality or hospitalization for heart failure within 12 months after randomization.
研究概览
简要总结
Atrial functional mitral regurgitation (AFMR) develops when enlargement and remodeling of the left atrium and mitral annulus prevent the mitral valve leaflets from closing completely, allowing blood to leak backward through the valve. For patients with significant AFMR who remain symptomatic despite medical treatment and are at high risk for surgery, it is uncertain whether adding transcatheter mitral valve edge-to-edge repair (TEER), a catheter-based procedure that brings the mitral valve leaflets together, provides better outcomes than medical treatment alone.
PRECISE-AFMR I is a prospective, multicenter, randomized study that will enroll 182 adults with moderate-to-severe or severe AFMR, high or prohibitive surgical risk, and mitral valve anatomy suitable for TEER. Participants will be assigned in a 1:1 ratio to receive TEER plus optimized guideline-directed medical therapy (GDMT) or optimized GDMT alone. All participants will receive standardized medical care and will be followed for 12 months.
The main effectiveness outcome is the occurrence of death from any cause or hospitalization for heart failure within 12 months. The main safety outcome is the occurrence of major device-related adverse events within 12 months. The study will also assess mitral regurgitation severity, symptoms, functional capacity, quality of life, heart failure events, and use of health care resources.
详细描述
PRECISE-AFMR I is designed to address the limited randomized evidence for transcatheter edge-to-edge repair (TEER) in patients with atrial functional mitral regurgitation (AFMR). The study uses standardized phenotypic and imaging assessment to identify patients in whom AFMR is the predominant mechanism of mitral regurgitation and whose mitral valve anatomy is considered suitable for TEER.
Before randomization, each participant will provide written informed consent and undergo clinical, laboratory, and imaging assessments. Echocardiographic data will be submitted to an independent echocardiography core laboratory (ECL) for confirmation of the AFMR diagnosis, mitral regurgitation severity, left ventricular function, left atrial remodeling, and anatomical suitability for TEER. An eligibility committee will then review the clinical findings, surgical risk, prior treatment, and ECL assessment. Only participants confirmed as eligible by both the ECL and the eligibility committee will proceed to randomization.
Eligible participants will be randomly assigned in a 1:1 ratio to TEER plus optimized guideline-directed medical therapy (GDMT) or optimized GDMT alone. Randomization will be performed through a central randomization system or electronic data capture system using blocked randomization stratified by study center or center group. The allocation sequence will be generated and maintained independently, and treatment assignment will not be released until eligibility and baseline assessments have been completed.
Because TEER is an interventional procedure, participants and treating investigators will not be blinded to treatment assignment. To reduce potential assessment bias, key echocardiographic measurements will be centrally reviewed by the ECL, and major clinical and safety events will be adjudicated by an independent clinical events committee that is blinded to treatment assignment whenever feasible. Both groups will receive comparable follow-up intensity, event collection, heart failure management, atrial fibrillation management, anticoagulation or antiplatelet therapy when clinically indicated, and management of comorbid conditions.
Participants assigned to the TEER group will undergo the procedure in addition to continued optimized GDMT and standardized clinical care. TEER is intended to be performed as soon as clinically feasible after randomization, preferably within 14 days and, when medically delayed, within 30 days whenever possible. Participants assigned to the control group will not undergo planned TEER before completion of the 12-month primary evaluation period and will receive individualized optimization of GDMT and other indicated standard treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The independent Clinical Events Committee will adjudicate major efficacy and safety events without knowledge of treatment assignment whenever feasible. Key echocardiographic assessments will be centrally reviewed by an independent echocardiography core laboratory using standardized procedures.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Aged ≥18 years;
- •2. Presence of symptoms of heart failure, with New York Heart Association (NYHA) functional class II, III, or ambulatory class IV;
- •3. Confirmed by preliminary assessment of the study-site Heart Team and review by the Echocardiography Core Laboratory (ECL) to have at least moderate-to-severe atrial functional mitral regurgitation (AFMR), generally graded as 3+ or 4+;
- •4. At least one hospitalization for heart failure within the 12 months prior to enrollment and/or a plasma B-type natriuretic peptide (BNP) level ≥300 pg/mL or N-terminal pro-B-type natriuretic peptide (NT-proBNP) level ≥1,500 pg/mL;
- •5. As confirmed by a heart failure specialist at the study site, the subject has received maximally optimized guideline-directed medical therapy (GDMT) and other necessary standardized comprehensive treatment in accordance with current guidelines for at least 3 months. For subjects with concomitant atrial fibrillation, coronary artery disease, or other potentially correctable comorbidities, appropriate evaluation and guideline-recommended management must have been completed, or the subject must have been clearly determined to be unsuitable for further treatment;
- •6. Determined by the multidisciplinary Heart Team, in accordance with the process described in Section 4.7, to be at high surgical risk, to have a contraindication to surgery, or to be unsuitable for surgery, or determined after comprehensive assessment that surgical treatment is not the optimal current strategy;
- •7. During the screening period or within 90 days prior to randomization, mitral valve anatomy is assessed by echocardiography at the study site and confirmed by the ECL to be suitable for transcatheter edge-to-edge repair (TEER). Anatomical suitability must meet at least all of the following criteria:
- •Mitral valve area >4.0 cm² and baseline mean transmitral pressure gradient <4 mmHg;
- •Adequate mobility or sufficient graspable leaflet tissue in the target grasping area, with a mobile/graspable leaflet length ≥10 mm;
- •Mitral annular anteroposterior diameter ≤40 mm;
- •Left atrial volume index (LAVI) <85 mL/m²;
- •⑤ Leaflet-to-annulus index (LAI) >1.10;
- •8. The transseptal puncture route and femoral venous access are considered suitable for TEER by the investigator or Heart Team;
- •9. The subject or the subject's legally authorized representative voluntarily agrees to comply with the requirements of the study protocol, including the possibility of being randomized to the optimized GDMT group, and provides written informed consent.
排除标准
- •1. Presence of primary structural mitral valve disease that can independently account for the mitral regurgitation (MR), such as leaflet prolapse, flail leaflet, rheumatic valvular disease, leaflet perforation, or damage resulting from infective endocarditis;
- •2. Functional mitral regurgitation other than atrial functional mitral regurgitation (AFMR), including ventricular functional mitral regurgitation caused by left ventricular dilatation, regional wall-motion abnormalities, ischemic cardiomyopathy, dilated cardiomyopathy, or other conditions involving the myocardium, including restrictive cardiomyopathy, hypertrophic cardiomyopathy, and infiltrative cardiomyopathy such as amyloidosis, hemochromatosis, or sarcoidosis;
- •3. Presence of pericardial disease, such as constrictive pericarditis, that may be the predominant mechanism underlying heart failure or MR;
- •4. Prior surgical mitral valve intervention or transcatheter mitral valve intervention;
- •5. Concomitant moderate-to-severe or greater disease of another heart valve requiring surgical or transcatheter intervention;
- •6. An acute cerebrovascular event within the previous 30 days;
- •7. Cardiovascular or cerebrovascular surgery or interventional treatment within the previous 30 days, including coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), transcatheter aortic valve replacement (TAVR), or transcatheter carotid artery stenting;
- •8. Severe symptomatic carotid artery stenosis, defined as >70% stenosis on ultrasonography;
- •9. Hemodynamic instability requiring continuous intravenous drug infusion or mechanical circulatory support;
- •10. Pulmonary artery systolic pressure (PASP) >70 mmHg as estimated by echocardiography, or pulmonary vascular resistance (PVR) >3 Wood units as measured by right heart catheterization;
- •11. Symptoms, signs, or echocardiographic evidence of severe right ventricular dysfunction, such as tricuspid annular plane systolic excursion (TAPSE) <15 mm or peak systolic tissue Doppler velocity (S') <10 cm/s;
- •12. Chronic renal insufficiency requiring long-term hemodialysis;
- •13. Severe liver cirrhosis accompanied by esophageal varices;
- •14. Prior heart transplantation;
- •15. Severe chronic obstructive pulmonary disease (COPD) requiring continuous home oxygen therapy or long-term oral glucocorticoid therapy;
- •16. Severe hematologic disease;
- •17. A modified Rankin Scale score ≥4, indicating moderately severe or severe disability;
- •18. Mitral valve anatomical features that, as assessed by echocardiography at the study site and confirmed by the Echocardiography Core Laboratory (ECL), may prevent safe implantation, appropriate positioning, stable leaflet grasping, or adequate reduction of MR with the transcatheter edge-to-edge repair (TEER) device. Such features include, but are not limited to, insufficient leaflet mobility or insufficient graspable leaflet tissue in the target grasping area, significant calcification in the grasping area, a prominent leaflet cleft, leaflet perforation, severe leaflet thickening, fibrosis, retraction, or severely restricted leaflet mobility, insufficient primary or secondary chordal support, or any other anatomical feature that, in the judgment of the ECL, may result in technical failure of TEER, significant residual MR, or an increased risk of clinically significant mitral stenosis after the procedure;
- •19. An intracardiac mass, thrombus, or vegetation detected by echocardiography;
- •20. A contraindication to, or a high risk associated with, transesophageal echocardiography;
- •21. Inadequate echocardiographic image quality;
- •22. Known allergy or contraindication to any medication or device material required for the TEER procedure;
- •23. Pregnancy, breastfeeding, or intention to become pregnant within the following 12 months;
- •24. Anticipated need for emergency surgery or elective cardiac surgery for any reason within the following 12 months;
- •25. Life expectancy of <12 months due to a noncardiac condition;
- •26. The subject is a member of a vulnerable population or has a condition that may impair their ability to provide written informed consent and/or comply with study procedures;
- •27. Current participation in another interventional drug or device trial that may interfere with the assessment of the primary endpoint of this study;
- •28. Any other condition that, in the judgment of the investigator, ECL, or EC, renders the subject unsuitable for participation in this study.
结局指标
主要结局
Composite endpoint of all-cause mortality or hospitalization for heart failure within 12 months after randomization.
时间窗: Within 12 months after randomization.
Composite endpoint of device-related major adverse events.
时间窗: Within 12 months after randomization.
* Single leaflet device attachment (SLDA); * Device migration, device embolization, device detachment, or device fracture; * Device thrombosis; * Device-related infective endocarditis; * Mitral stenosis requiring surgical treatment or an unplanned repeat intervention; * Non-elective cardiac surgery or unplanned repeat mitral valve intervention due to a device-related complication; * Left ventricular assist device implantation; * Heart transplantation; * Other serious device-related complications adjudicated by the Clinical Events Committee (CEC) as device-related major adverse events in accordance with the Mitral Valve Academic Research Consortium (MVARC) criteria.
次要结局
- Hierarchical composite endpoint of all-cause mortality, hospitalization for heart failure, or urgent emergency department/outpatient intensification of heart failure therapy within 12 months after randomization(within 12 months after randomization)
- Proportion of patients with MR ≤1+ at 30 days, 6 months, and 12 months(30 days, 6 months, and 12 months)
- Proportion of patients with MR ≤2+(30 days, 6 months, and 12 months)
- Residual MR grade and change from baseline(30 days, 6 months, and 12 months)
- Change in NYHA functional class and proportion of patients in NYHA class I/II(30 days, 6 months, and 12 months)
- Change from baseline in left atrial anteroposterior diameter(at 12 months)
- Change from baseline in left atrial volume index (LAVI)(at 12 months)
- Change from baseline in 6-minute walk distance (6MWD)(at 12 months)
- Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score(at 12 months)
- Change from baseline in BNP or NT-proBNP level(at 12 months)
- Number of recurrent hospitalizations for heart failure(within 12 months after randomization)
- All-cause mortality(within 12 months after randomization)
- Cardiovascular mortality(within 12 months after randomization)
- Non-cardiovascular mortality(within 12 months after randomization)
- First hospitalization for heart failure(within 12 months after randomization)
- Total number of hospitalizations for heart failure(within 12 months after randomization)
- Emergency department visits or outpatient events requiring intensification of heart failure therapy(within 12 months after randomization)
- Composite endpoint of major procedure-related adverse events(within 30 days after the TEER procedure)