Achieving Optimal Medical Therapy Through Percutaneous Treatment of Secondary Mitral Regurgitation to Improve Outcome in Patients With HFrEF
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 520
- 主要终点
- Difference in Guideline-Directed Medical Therapy (GDMT) Score at 12 Weeks
研究概览
简要总结
The purpose of the ACHILLES-HF trial (ACHIeving optimaL medicaL therapy through pErcutaneous treatment of Secondary mitral regurgitation to improve outcome in Patients with Heart Failure with reduced ejection fraction) is to test whether early transcatheter edge-to-edge repair (TEER) in patients with heart failure and reduced ejection fraction (HFrEF) and relevant secondary mitral regurgitation, that are at risk of not receiving full guideline recommended therapy (GDMT), results in faster and more complete GDMT up-titration and whether this translates into improved quality of life and clinical outcomes.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%)
- •Clinically significant functional mitral regurgitation (moderate-to severe or severe MR) as defined by European Association of Echocardiography, within 90 days prior to randomization (i.e. EROA ≥0.2 cm² and/or regurgitant fraction >30%)
- •Suboptimal GDMT therapy corresponding to a GDMT score <7 points
- •Risk factor for not intensification of guideline directed medical therapy (at least one of the following):
- •Office systolic blood pressure <120 mmHG
- •Chronic renal failure with eGFR <60 ml/min/1.73m
- •History of acute kidney injury (AKI) at least stage 2 within the last 12 months
- •Serum Potassium ≥ 4.8 mmol/L
- •Persisting symptoms equalling NYHA functional class II-IVa (ambulatory)
- •Patient has had at least one HF hospitalization within 12 months and/or a NT-proBNP ≥1000 pg/ml
- •Interventional cardiologist believes secondary MR can be successfully treated by an interventional approach
- •The subject has been informed of the nature of the study and agrees to the study's provisions, including the possibility of randomization to the Control group, and has provided written informed consent as approved by the respective clinical site's Ethics Committee
排除标准
- •Terminal heart failure or hemodynamic instability
- •Primary TR or MR, any other severe valvular heart disease
- •Untreated clinically significant CAD (coronary artery disease) requiring revascularization
- •LVEF <35% and left bundle branch block with a QRS duration >150 ms
- •Renal failure requiring dialysis
- •Mitral valve orifice area <4.0 cm² by site assessed TTE
- •Life expectancy <12 months due to non-cardiac conditions
- •KCCQ score > 80 points
- •Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated)
- •Active infections requiring current antibiotic therapy.
- •Known hypersensitivity or contraindication to procedural device which cannot be adequately managed medically.
- •Patient is pregnant, nursing, or planning to be pregnant
- •Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the investigator.
- •Currently participating in another investigational therapeutic or interventional clinical trial, or in any trial of an unapproved drug, device or procedure. Note: Subjects participating in observational studies or registries may be considered as eligible.
- •Ineligibility to consent
研究组 & 干预措施
Intervention group
Subjects randomized to this arm undergo transcatheter edge-to-edge repair (M-TEER) of the mitral valve within 7 days of randomization, in addition to a standardized, protocol-driven guideline-directed medical therapy (GDMT) up-titration regimen. Starting on the first post-procedural day, subjects are up-titrated toward optimal target doses of a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor, guided by protocol-defined thresholds for blood pressure, heart rate, potassium, and renal function, with formal safety/tolerability reassessment at 2, 4, 6, 8, 10, and 12 weeks.
干预措施: M-TEER (Device)
Intervention group
Subjects randomized to this arm undergo transcatheter edge-to-edge repair (M-TEER) of the mitral valve within 7 days of randomization, in addition to a standardized, protocol-driven guideline-directed medical therapy (GDMT) up-titration regimen. Starting on the first post-procedural day, subjects are up-titrated toward optimal target doses of a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor, guided by protocol-defined thresholds for blood pressure, heart rate, potassium, and renal function, with formal safety/tolerability reassessment at 2, 4, 6, 8, 10, and 12 weeks.
干预措施: Standardized GDMT Up-Titration (Other)
Control group
Subjects randomized to this arm receive the identical standardized, protocol-driven GDMT up-titration regimen as the Intervention group, without early M-TEER. Up-titration toward optimal target doses of a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor begins at randomization and follows the same protocol-defined safety thresholds and visit schedule (2, 4, 6, 8, 10, and 12 weeks) as the Intervention group. Subjects may cross over to M-TEER or mitral valve surgery after completion of the 12-week follow-up visit, or earlier in the case of an intervening heart failure hospitalization.
干预措施: Standardized GDMT Up-Titration (Other)
结局指标
主要结局
Difference in Guideline-Directed Medical Therapy (GDMT) Score at 12 Weeks
时间窗: Baseline and 12 weeks post-randomization (post-procedure for Intervention group)
Between-group difference in GDMT intensity score, a 0-12 point composite scoring dosing of ACE inhibitor/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor relative to trial-defined target doses (0-\[2\]3 points per drug class). Analyzed via a mixed model for repeated measures (fixed effects for site, age group, sex, NYHA class, treatment, visit, and treatment-by-visit interaction; baseline score as covariate; first-order autoregressive covariance structure). Higher scores indicate more complete guideline-directed therapy.
Difference in Quality of Life (KCCQ Score) at 12 Weeks
时间窗: Baseline and 12 weeks post-randomization (post-procedure for Intervention group), among surviving patients
Between-group difference in quality of life among surviving patients, assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score (range 0-100, higher scores indicate better health status), from baseline to 12 weeks. Analyzed via two-sample t-test.
Composite of Cardiovascular Death or First Heart Failure Hospitalization at 24 Months
时间窗: From randomization to 24 months
Time to the first occurrence of cardiovascular death or heart failure hospitalization within 24 months of randomization, centrally adjudicated by an independent Clinical Events Committee blinded to treatment allocation.
次要结局
- Win Ratio for Cardiovascular Mortality, First Heart Failure Hospitalization, KCCQ Improvement, or GDMT Score Improvement at 24 Months(From randomization to 24 months (GDMT and KCCQ improvement assessed at 12 weeks))
- Total Heart Failure Hospitalizations Through 24 Months(From randomization to 24 months)
- Mitral Regurgitation Severity at 24 Months(24 months)
- NYHA Functional Class Improvement at 12 Months(Baseline and 12 months)
- Change in Left Ventricular End-Diastolic Volume (LVEDV) from Baseline to 12 Months(Baseline and 12 months)
- All-Cause Mortality Within 24 Months(From randomization to 24 months)
- Need for Mitral Valve Re-Intervention(From randomization to 24 months)
研究者
Philipp Lurz
Professor of Medicine, Director of the Department of Cardiology
University Medical Center Mainz