Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in Patients With Heart Failure With Preserved Ejection Fraction Monitored With the CardioMEMS Device (ARNIMEMS-HFpEF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Change in mPAP With Sacubitril/Valsartan compared to Standard therapy
研究概览
简要总结
This study will assess the impact of sacubitril/valsartan on elevated pulmonary artery (PA) pressures in patients with heart failure (HF) with preserved ejection fraction (HFpEF), measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
详细描述
Fluid overload leading to increased PA pressure is one of the primary causes of HF related hospitalizations in HFpEF. Signs and symptoms of fluid overload are not sensitive enough to reflect early pathophysiologic changes that increase the risk of decompensation. Elevations in PA pressure may increase several days or weeks before signs and symptoms manifest.
The CardioMEMS device is a small wireless sensor that is permanently implanted in the PA via a catheter inserted through the femoral vein. The sensor measures PA pressure and is paired with a portable electronic transmitter. The system allows patients to wirelessly transmit pressure readings to a secure online database from which treating physicians can access the data and adjust medication in response to PA pressure changes.
The CHAMPION trial was a single blind randomized clinical trial that showed a significant and large reduction in hospitalizations in patients with NYHA class III HF who were managed with a the CardioMEMS device.
More recently, real life clinical practice has confirmed the value of PA pressure-guided therapy for HF. PA pressures were reduced, lower rates of HF hospitalizations and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HF hospitalizations were reported.
The angiotensin receptor-neprilysin inhibitor (ARNI) led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and reduced ejection fraction in the PARADIGM-HF trial. However it did not result in a significantly lower rate of total hospitalizations for HF and death from cardiovascular causes among patients with HF and an ejection fraction of 45% or higher in the PARAGON-HF trial, despite there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients able to provide written informed consent.
- •Patients ≥18 years of age, male or female, in NYHA Class II- III HFpEF with LVEF > 45% (measured within the past year), and who have no previous LVEF<45%.
- •NT-proBNP >200 pg/ml if HF hospitalization in the previous 9 months and> 300 pg/ml if there was no previous HF hospitalization; Three times the values were required in patients with atrial fibrillation.
- •CardioMEMS HF System implanted and patient transmitting information regularly and system functioning appropriately.
- •Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 5 daily measurements.
- •Systolic BP > 100 mm Hg at most recent clinical assessment.
- •Stable, ambulatory patients without the need for change in diuretics and other HF drugs during last week.
排除标准
- •eGFR < 30 ml/min/1.73 m2 as measured by CKD-EPI.
- •Sacubitril/Valsartan treatment within the past 30 days.
- •History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- •Serum potassium > 5.4 mmol/L.
- •Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.
- •Coronary or carotid artery disease likely to require surgical or percutaneous intervention within 3 months after trial entry.
- •Non-cardiac condition(s) as the primary cause of dyspnea.
- •Documented untreated ventricular arrhythmia with syncopal episodes within the prior 3 months.
- •Symptomatic bradycardia or second or third degree heart block without a pacemaker.
- •Hepatic dysfunction, as evidenced by total bilirubin > 3 mg/dl.
- •Pregnancy.
- •Women who are breastfeeding
研究组 & 干预措施
Treatment
All the subjects will receive sacubitril/valsartan from weeks 6 to 12. From weeks 1-6 and 12-18 patients will be treated with standard therapy for HFpEF according to PA pressures (diuretics and systemic vasodilators if concomitant hypertension).
All the subjects will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).
Device: Patients eligible for this study are those with an already implanted CardioMEMS device.
Drug: Sacubitril/Valsartan Target dose:97/103mg bid
干预措施: Sacubitril / Valsartan Oral Tablet [Entresto] (Drug)
结局指标
主要结局
Change in mPAP With Sacubitril/Valsartan compared to Standard therapy
时间窗: Time Frame: 0-18 weeks
Change in Mean Pulmonary Artery Pressure With Sacubitril/Valsartan compared to Standard therapy.
次要结局
- Change in E/e'(6 weeks, 12 weeks, 18 weeks)
- Change in septal e' velocity(6 weeks, 12 weeks, 18 weeks)
- Change in the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)(Baseline, 18 weeks)
- Change in Daily Diuretic Dose(Baseline-6-12-18 weeks)
- Mean Change in mPAP(7 days)
- Change in Distance Walked(Baseline, 6 weeks, 12 weeks, 18 weeks)
- Change in NT-proBNP concentration(6-12-18 weeks)
- Change in CA-125 concentration(6-12-18 weeks)
- Decline in renal function(Baseline-18 weeks)
- Change in Soluble ST2 concentration(6-12-18 weeks)
- Change in the European Quality of Life-5 Dimensions scale(Baseline, 18 weeks)
- Change in lateral e' velocity(6 weeks, 12 weeks, 18 weeks)
- Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity(6 weeks, 12 weeks, 18 weeks)
- Change in diastolic dysfunction echocardiography parameter left atrium volumen index(6 weeks, 12 weeks, 18 weeks)
- Change in the number of B-lines in lung ultrasound LUS(6 weeks, 12 weeks, 18 weeks)
- Prespecified adverse events of interest(Baseline-18 weeks)