Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 450
- 试验地点
- 71
- 主要终点
- All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score.
研究概览
简要总结
This is a prospective, multicenter, open-label, randomized trial comparing mitral valve (MV) transcatheter edge-to-edge repair (TEER) to surgical repair (1:1 ratio) in patients with primary, degenerative mitral regurgitation (MR). The trial will be conducted in the U.S., Canada, Germany, Spain, and the United Kingdom, and is designed as a strategy trial. Thus, all devices legally marketed for TEER of primary degenerative MR in a particular country are eligible to be used in this trial.
详细描述
The primary aim of this study is to evaluate the long-term effectiveness and safety of MV TEER compared with surgical repair in patients with primary, degenerative MR. The secondary aim is to analyze the relationship between the adequacy of MR correction at one-year post intervention and longer-term clinical outcomes (death, heart failure hospitalizations/urgent care visits, valve re-interventions, and quality of life). The tertiary aim of this trial is to evaluate a range of patient-centered outcomes (quality of life, functional status, and discharge location) of transcatheter edge-to-edge MV repair compared with MV surgical repair in patients with primary, degenerative mitral regurgitation. This study is closely integrated with the PRIMARY Ancillary Substudy (NCT07103733)
The patient population for this trial consists of adult patients with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible.
Because the use of the commercial edge-to-edge mitral repair device in the U.S. is approved only in patients considered to be at prohibitive risk of MV surgery by a heart team, use of such devices in this trial is considered investigational by the FDA. As such, this trial will be conducted under an Investigational Device Exemption (IDE).
Outcomes will be measured from randomization over a period of 5 years post intervention. The estimated enrollment period is 36 months, and all patients will be followed from randomization for up to 10 years post intervention for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.
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
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient population for this trial consists of adults with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible. Specific inclusion and
排除标准
- •are listed below. All patients who meet eligibility criteria will be included in the study regardless of gender, race, or ethnicity.
- •Inclusion Criteria:
- •Adult patients ≥60 years with moderately-severe or severe (3+ or 4+/4+) primary degenerative (Carpentier type II) MR defined by transthoracic echocardiography
- •Clinical indication for MV intervention and anatomic candidate for both surgical MV repair and transcatheter edge-to-edge repair (TEER) per local heart team assessment with central eligibility committee verification
- •Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on local heart team assessment and central eligibility committee verification (see ACC/AHA 2020 guidelines for the management of patients with valvular heart disease)
- •Patients with AF who meet an indication for a concomitant ablation procedure be included provided the local heart team and central eligibility committee decide they are eligible for both catheter-based and surgical ablation.
- •Ability to perform 6-minute walk test (6MWT) and complete Kansas City Cardiomyopathy Questionnaire (KCCQ) instrument
- •Exclusion Criteria:
- •Non-degenerative types of primary MR (e.g., cleft leaflet)
- •Secondary or functional MR
- •Hypertrophic obstructive cardiomyopathy
- •Presence of an IVC filter or permanent pacing/ICD leads that would interfere with TEER per local heart team assessment
- •Known allergic reactions to intravenous contrast
- •Febrile illness within 30-days prior to randomization
- •Any absolute contraindication to transesophageal echocardiography
- •Any contraindication to systemic heparinization including active bleeding diatheses, and heparin induced thrombocytopenia
- •Patients with CAD requiring revascularization
- •Any prior mitral valve intervention or any prior repair of atrial septal defect
- •Any prior MV intervention or any prior repair of atrial septal defect
- •Need for any of the following concomitant procedures: aortic valve or aortic surgery, tricuspid valve surgery
- •Need for any emergency intervention or surgery
- •Active endocarditis
- •Hemodynamic instability defined as cardiac index <2.0 l/min/m2 or systolic blood pressure <90mmHg or need for inotropic support or any mechanical circulatory support
- •Left ventricular ejection fraction <25%
- •Intracardiac mass or thrombus
- •Co-morbid medical or oncologic condition for which local heart team believes that survival beyond 2 years is unlikely
- •Active substance abuse
- •Suspected inability to adhere to follow-up
- •Treatment with another investigational drug or other intervention, assessment of which has not completed the primary endpoint or that clinically interferes with the present study endpoints.
研究组 & 干预措施
Transcatheter edge-to-edge repair
In the transcatheter edge-to-edge repair arm, patients will be treated with a commercially-approved edge-to-edge mitral repair device.
干预措施: Transcatheter edge-to-edge repair (Device)
Surgical mitral valve repair
Patients who are randomized to the surgical arm will undergo mitral surgery.
干预措施: Mitral valve repair (Procedure)
结局指标
主要结局
All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score.
时间窗: 3 years post intervention
All-cause mortality, valve re-intervention, hospitalizations/urgent visits for heart failure (without a blanking period), or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum of 3 years post intervention. Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean.
All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score.
时间窗: 3 years post intervention
Composite score of all-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum follow-up of 3 years post randomization (including a one-month post intervention blanking period for HF hospitalizations/urgent visits). Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean.
次要结局
- ICU days of index hospitalization(through 10 years post intervention)
- Number and reasons for readmissions(through 10 years post intervention)
- Cost(through 10 years post intervention)
- Cost-effectiveness(through 10 years post intervention)
- Number of participants with stroke with disability(30 days post-intervention)
- Kansas City Cardiomyopathy Questionnaire (KCCQ)(up to 10 years post intervention)
- Valve re-interventions(10 years post intervention)
- 6 Minute Walk Test (6MWT)(up to 5 years post intervention)
- EuroQol- 5 Dimension (EQ-5D)(through 10 years post intervention)
- Length of stay (LOS)(through 10 years post intervention)
- MR grade(up to 5 years post intervention)
- Adequacy of MR correction(one year post intervention)
- Kansas City Cardiomyopathy Questionnaire (KCCQ)(up to 10 years post intervention)
- Procedure failure(10 years post randomization)
- All-cause mortality(10 years post intervention)
- Cardiovascular and non-cardiovascular mortality(10 years post intervention)
- Valve re-interventions(10 years post intervention)
- Serious or protocol-defined adverse events(5 years post intervention)
- Left Ventricular End Systolic Dimension (LVESD)(up to 5 years post intervention)
- Left Ventricular End Systolic Volume (LVESV)(up to 5 years post intervention)
- Cost(through 10 years post intervention)
- Mitral valve gradient(up to 5 years post intervention)
- Forward stroke volume(up to 5 years post intervention)
- 6 Minute Walk Test (6MWT)(up to 5 years post intervention)
- EuroQol- 5 Dimension (EQ-5D)(through 10 years post intervention)
- Length of stay (LOS)(through 10 years post intervention)
- ICU days of index hospitalization(through 10 years post intervention)
- Number and reasons for readmissions(through 10 years post intervention)
- Cost-effectiveness(through 10 years post intervention)
- Number of participants with stroke with disability(30 days post-intervention)
- Forward stroke volume(up to 6 years post intervention)
- Procedure failure(End of procedure)
- All-cause mortality(5 years post randomization)
- Cardiovascular and non-cardiovascular mortality(5 years post intervention)
- Valve re-interventions(5 years post intervention)
- MR grade(up to 6 years post intervention)
- Left Ventricular Ejection Fraction (LVEF)(up to 6 years post intervention)
- Left Ventricular End Diastolic Dimension (LVEDD)(up to 6 years post intervention)
- Left Ventricular End Systolic Dimension (LVESD)(up to 6 years post intervention)
- Left Ventricular End Diastolic Volume (LVEDV)(up to 6 years post intervention)
- Left Ventricular End Systolic Volume (LVESV)(up to 6 years post intervention)
- Mitral valve gradient(up to 6 years post intervention)
研究者
Annetine Gelijns
Chair, Department of Population Health Science & Policy Edmond A. Guggenheim Professor of Health Policy Co-Director, InCHOIR
Icahn School of Medicine at Mount Sinai