Prospective Comparison of ARNI to Alternate Oral Vasodilator Therapies to Determine the Hemodynamic Profile and Relative Tolerability of (ARNIs) in Patients With Decompensated Heart Failure and Low Cardiac Output
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Proportion of patients on ARNI therapy at one-month follow-up
研究概览
简要总结
This is a prospective, randomized, non-blinded, single-center efficacy study of acutely decompensated heart failure patients with reduced ejection fraction (HFrEF), low cardiac index (<2.2) as determined by pulmonary artery catheter (PAC) who have been hemodynamically stabilized and ready for transition to oral vasodilator therapy at the discretion of the clinician. The investigators would like to accomplish the following objectives with this study:
- Establish the superiority of an upfront initiation strategy for sacubitril-valsartan at maintaining patients on ARNI therapy at one-month follow-up compared to usual care.
- Establish the safety of initiating sacubitril-valsartan in an intensive care setting
- Characterize the hemodynamic effect of sacubitril-valsartan on patients with low cardiac output
- Expand the population of hospitalized patients that can be initiated on ARNIs and thus facilitate prior to hospital discharge patients who are on optimal goal-directed medical therapy (GDMT) for heart failure
详细描述
This is a prospective, randomized, non-blinded, single-center efficacy study of acutely decompensated heart failure patients with reduced ejection fraction (HFrEF), low cardiac index (<2.2) as determined by pulmonary artery catheter (PAC) who have been hemodynamically stabilized and ready for transition to oral vasodilator therapy at the discretion of the clinician. The investigators would like to accomplish the following objectives with this study:
- Establish the superiority of an upfront initiation strategy for sacubitril-valsartan at maintaining patients on ARNI therapy at one-month follow-up compared to usual care.
- Establish the safety of initiating sacubitril-valsartan in an intensive care setting
- Characterize the hemodynamic effect of sacubitril-valsartan on patients with low cardiac output
- Expand the population of hospitalized patients that can be initiated on ARNIs and thus facilitate prior to hospital discharge patients who are on optimal goal-directed medical therapy (GDMT) for heart failure
In this pragmatic study, the primary endpoint will be establishing the superiority of sacubitril-valsartan as an oral vasodilator in maintaining ARNI therapy at one-month post hospital discharge as compared to usual care. Given the overall mortality and heart failure hospitalization benefit of ARNI over ACEI and other vasodilators has been established in large-scale clinical trials, establishing that upfront initiation of ARNI therapy in patients with low cardiac output is safe and can be maintained post-discharge would be of significant clinical benefit. Adverse events including symptomatic hypotension (requiring cessation of drug), development of worsening renal function (requiring cessation of drug), hyperkalemia [moderate (> 5.5 mmol/L) or severe (> 6 mmol/L)], or re-initiation of IV vasodilator or IV inotropic therapy will be monitored and tracked.
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 (EF <40%) documented in past 1 year
- •Presence of low cardiac index ≤2.2 based on PA catheter measurement followed by stabilization and readiness to transition to oral vasodilator therapy
- •SBP > 90 and SVR >950 at the time of randomization or tolerating an adequate amount of IV vasodilator therapy i.e. sodium nitroprusside (clinician discretion) without symptomatic or sustained hypotension (>30 minutes)
- •Intention to maintain pulmonary artery catheter for hemodynamic directed optimization of therapy
排除标准
- •Acute kidney injury (increase in serum creatinine concentration of >0.5 mg per deciliter) and a decrease in the estimated GFR >25% in the preceding 24 hours
- •Documented intolerance to sacubitril, valsartan, or any ARBs, neprilysin inhibitors or any of the sacubitril/valsartan excipients, any history of angioedema
- •End-stage renal disease at screening, or estimated GFR <30mL/min/1.73m² by MDRD
- •Sustained Symptomatic hypotension after initiation of nitroprusside (Clinician Discretion or >30 minutes)
- •Acute Coronary Syndrome, Stoke, TIA, Cardiac, Carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within 3 months of screening
- •Hyperkalemia- Serum Potassium >5.5 mmol/L at randomization
- •Enrollment in concurrent clinical trials with investigational drugs
- •CAD likely to require surgical or percutaneous intervention within 3 months after screening
- •Implantation ofCRT, or upgrade of existing device or revision of the device leads within 1 month of screening
- •Heart Transplant or VAD or intent to transplant (on transplant list) or implant VAD in the next 6 months.
- •PI discretion regarding eligibility
- •Active infection/sepsis
- •Active use of temporary mechanical support
研究组 & 干预措施
ARNI therapy
Patient's randomized to this arm will receive sacubitril-valsartan per study protocol and titrated per titration guidelines.
干预措施: Sacubitril-Valsartan (Drug)
Standard Oral Vasodilator
Patient's randomized to this arm will receive the oral vasodilator that the clinician chooses including angiotensin receptor blocker (ARB), isosorbide dinitrate, hydralazine, and angiotensin-converting enzyme inhibitor (ACEi).
干预措施: Standard Oral Vasodilators (Drug)
结局指标
主要结局
Proportion of patients on ARNI therapy at one-month follow-up
时间窗: 1 month
This will be the proportion of patients randomized to each arm who remain on ARNI therapy at one-month follow-up. Reasons for discontinuation will be tracked.
次要结局
- Length of time of in the Intensive Care Unit(Hospital discharge, 1 Month)
- 180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant(180 days)
- Length of Hospital Stay(Hospital discharge, 1 Month)
- Change in NT-proBNP from admission at one-month follow-up(1 Month)
- 30 day HF readmissions(1 Month)
研究者
Randall C Starling MD MPH
Principal Investigator
The Cleveland Clinic