A Multicenter, Randomized, Open-label, Parallel Group, Pilot Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension
研究概览
简要总结
The primary objective of this prospective randomised study is to assess the safety and tolerability of sacubitril/valsartan compared with standard of care used for treating BP in patients that have been implanted with the Heart Mate 3 LVAD (events of special interest - all cause death, right ventricular failure, bleeding events, deterioration in renal function, hyperkalemia, symptomatic hypotension).
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)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •≥18 years of age, male or female
- •Recently implanted HeartMate 3 LVAD recipients, in stable condition and deemed ready for discharge or chronic, stable, ambulatory HeartMate 3 LVAD carriers implanted within 1 year prior to enrolment
- •Current acute decompensated HF (including right ventricular failure) requiring therapy with intravenous diuretics or vasodilators and/or inotropic drugs within the past 48 hours
- •History of hypersensitivity to sacubitril/valsartan or to drugs of similar chemical classes, patients with a known history of angioedema
- •Patients with mean blood pressure ≤75 mmHg (systolic blood pressure i.e. Doppler opening blood pressure ≤90 mmHg in those pulsatile and measured by Doppler method) or symptomatic hypotension
- •eGFR < 30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at Visit 1
- •Patients with serum potassium >5.4 mmol/L (mEq/L) at Visit 1
- •Hemodynamically unstable patients or those with ongoing MCS other than LVAD or those with planned biventricular support
- •Hemodynamically significant aortic insufficiency in the opinion of the investigator
- •Irreversible end-organ dysfunction
- •Previous sacubitril/valsartan use while on LVAD support
- •Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within 30 days prior to enrolment
- •Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 bpm at enrolment
- •Any surgical or medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
- •Active infection with hemodynamic compromise
- •hemoglobin (Hgb) <8 g/dl
- •body mass index (BMI) > 45 kg/m2
- •Congenital heart disease
- •Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the 6 months after enrolment
- •Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x ULN, bilirubin >1.5 mg/dl at Visit 1
- •Pregnant or nursing (lactating) women and women of child-bearing potential unless they are using highly effective methods of contraception
排除标准
- 未提供
研究组 & 干预措施
sacubitril/valsartan
干预措施: Sacubitril-Valsartan (Drug)
Standard of care
Standard of care for treating blood pressure per center protocols
干预措施: Standard of care (Drug)
结局指标
主要结局
Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension
时间窗: 3 months
* End-stage renal disease defined as one of the following: 1. Initiation of dialysis (e.g., hemodialysis, peritoneal dialysis, or continuous venovenous hemodialysis), continuing for ≥ 20 days without known recovery of renal function 2. Initiation of dialysis with death before 30 days (excludes dialysis events associated with acute kidney injury with death before 30 days) 3. A drop in eGFR from baseline (randomization, i.e. Visit 101) to a value \<15 mL/min/1.73m2 on two consecutive measurements separated by≥ 20 days 4. Occurrence of kidney transplantation * 50% sustained decline in eGFR: 50% decline from baseline (Randomization, Visit 101) as determined by 2 consecutive post-baseline measurements separated by ≥ 20 days * Hyperkalemia: serum potassium ≥6.0 mmol/L \[mEq/L\]) Hypotension: symptomatic reduction in blood pressure requiring withdrawal of study medication or any BP lowering medication
次要结局
- Change in Burden of hemocompatibility (hemocompatibility score)(3 months, 12 months)
- Number of RV failure events(3 months, 12 months)
- Time to first unplanned hospitalisation(3 months, 12 months)
- Number of unplanned hospitalizations(3 months, 12 months)
- Change in blood-pressure lowering medications(3 months, 12 months)
- Change in eGFR values(3 months, 12 months)
- Change in NT-proBNP from enrolment to 8 weeks(8 weeks)
研究者
Maja Cikes
Associate professor, MD, PhD
University of Zagreb