Feasibility Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device (SCD) to Treat ICU Patients With Acute on Chronic Systolic Heart Failure With Worsening Renal Function Due to Cardiorenal Syndrome or Severe Right Ventricular Failure Awaiting Left Ventricular Assist Device Implantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
Cardiovascular disease is the leading cause of mortality in the US, accounting for 45% of all deaths. Chronic Heart Failure (CHF) is now understood to be a multi-system disease process involving not only the cardiovascular system but also the renal, neuroendocrine, and immune systems. No effective therapy is currently available to treat the most severe subset of CHF patients that have progressed to acute decompensated HF. An innovative approach to reduce the cardio-depressant effects associated with the chronic inflammatory state of CHF may provide a breakthrough for this disorder. This proposal will evaluate the safety and probable benefit to improve cardiac or renal function with an immunomodulatory device to bridge patients to Left Ventricular Assist Device (LVAD) implantation who were previously deemed ineligible for this life sustaining procedure. The Selective Cytopheretic Device (SCD) is an immuno-regulating, extracorporeal membrane device targeted to modulate the cardiodepressant effects assocaited with CHF. SCD is a platform technology focused on immunomodulation of acute and chronic inflammation associated with acute and chronic organ dysfunction. SCD membranes selectively sequester activated systemic leukocytes as they flow through the cartridge via an extracorporeal circuit. Pre-clinical results show that SCD treatment results in a 25% improvement in ejection fraction in a canine CHF model.
This study will enroll 20 patients across up to 5 clinical sites to evaluate the safety and initial efficacy data of SCD treatment in this indication. Patients will receive 4-hour daily SCD treatment for up to 6 days, followed by 6 months of follow up.
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
- •Age of 18 years and older.
- •Evidence of systemic inflammation: blood CRP ≥ 4.5 mg/L or IL-6 ≥ 5.0 pg/ml or neutrophil to lymphocyte ratio ≥3.
- •Primary hospitalization for acute decompensated chronic systolic heart failure.
- •Potential LVAD candidate with:
- •a) Left ventricular ejection fraction ≤25% (for potential destination therapy) or ≤ 35% (for potential bridge to transplantation) as confirmed by baseline imaging procedure b) NYHA class IIIB or IV chronic (≤ 90 days) systolic heart failure, with failure to respond to optimal medical therapy (beta blocker, ACE inhibitor or ARB or valsartan/sacubitril, aldosterone antagonist, SGLT2i, unless not tolerated or contraindicated, and loop diuretic, as needed) for 45 of the last 60 days c) Known previous peak exercise oxygen consumption < 14 mL/Kg/min or if unable to exercise, dependent on an intra-aortic balloon pump, short-term mechanical circulatory support device or intravenous inotropes unless inotropes contraindicated for clinical reasons (e.g., ventricular arrhythmias)
- •Baseline eGFR** ≥ 40 ml/min/1.73 m2 (baseline defined as the highest known eGFR within 90 days of study enrollment)
- •At least one of the following two criteria:
- •Severe right ventricular failure (RVF), defined as meeting at least 2 of the following 4 criteria -Central venous pressure > 16 mmHg
- •Central venous pressure/Pulmonary wedge pressure >0.65
- •Right ventricular stroke work index < 300 mmHg * ml/m2
- •Pulmonary artery pulsatility index (PAPi) < 2,
- •Worsening renal failure (WRF), defined for the purposes of this study as -Increase serum creatinine ≥ 0.5 mg/dL from baseline (baseline defined as the lowest known serum creatinine within 90 days of study enrollment) AND
- •eGFR** ≤ 30 ml/min/1.73 m2 based on serum creatinine at enrollment*** AND
- •Cardiorenal syndrome is the most likely explanation for WRF AND
- •Intolerant or inadequately responsive to standard of care diuretic therapy, defined as persistent signs and/or symptoms of congestion (e.g., peripheral edema, dyspnea, pulmonary rales, neck vein distension) or minimal net volume removal in a 24-hour period despite optimal medical therapy including intravenous diuretic therapy and an estimated need for >5kg fluid removal.
- •Optimal intravenous diuretic therapy is defined as:
- •Furosemide equivalent total daily dose of 240mg
- •Furosemide equivalent dose given either as a single or multiple intravenous bolus or continuous infusion
- •A furosemide equivalent total daily dose <240mg if the dose has resulted in >3000 mL urine output/24 hours.
- •PA catheter in place at the time of enrollment
- •PCW ≥ 20 mmHg
- •eGFR calculated using the CKD-EPI Creatinine Equation *** Recognizing that this is not a steady state creatinine
排除标准
- •Any clear contraindication to LVAD therapy that is unlikely to resolve with improvement in renal function and volume status
- •Prior sensitivity to dialysis device components
- •Active bacteremia
- •Temperature ≥ 101.5 F or WBC ≥ 10,000 K/uL or any patient with suspected systemic infection.
- •Metastatic malignancy requiring palliative chemo, biologic, or radiation
- •Need for intravenous vasopressor (i.e., phenylephrine, vasopressin), intravenous vasoconstricting inotrope (i.e., norepinephrine or epinephrine) or dopamine > 3 mcg/kg/min. (Note: use of vasodilating inotropes [i.e., dobutamine and milrinone] or dopamine at ≤ 3 mcg/kg/min will not preclude study inclusion)
- •Patients requiring mechanical ventilatory support
- •Patients requiring total parenteral nutrition during the treatment period
- •Persistent SBP < 80 mmHg
- •WBC < 4000 K/uL
- •Platelets < 100,000K/uL
- •Serum creatinine > 4 mg/dL or receiving dialysis / CRRT
- •Acute coronary syndrome within the past month
- •Women who are pregnant, breastfeeding a child, or trying to become pregnant
- •Concurrent enrollment in another interventional clinical trial. Patients enrolled in clinical studies where only measurements and/or samples are taken (i.e., no test device or test drug used) are allowed to participate
- •Use of any other investigational drug or device within the previous 30 days. Patients who participated in a clinical study where only measurements and/or samples are taken (i.e., no test device or drug used) are allowed to participate.
结局指标
主要结局
Adverse Events
时间窗: up to 6 days after initiation of SCD therapy
Adverse Events due to SCD, hemodialysis catheter, KRT pump, circuit, and hemofilter
Need for continuous IV vasopressor support
时间窗: measured daily, at or after 4 hours after termination of daily SCD therapy
Need for continuous IV vasopressor support with \>5 total norepinephrine equivalents and/or \>3 vasopressor agents \>4 hours following termination of daily SCD therapy session to maintain a MAP \>60 mmHg, with norepinephrine equivalents defined as: 1. 1 x epinephrine (ug/kg/min) 2. 001 x dopamine (ug/kg/min) 3. 0.06 x phenylephrine (ug/kg/min) 4. 2.5 x vasopressin (U/min) (Note that use of inotropes (i.e., dobutamine and milrinone) or dopamine at ≤3 mcg/kg/min are not components of this measure.)
Acute myocardial infarction
时间窗: up to 6 months following SCD treatment initiation
Acute myocardial infarction as evidenced by elevated cardiac enzymes, with electrocardiographic or imaging findings consistent with myocardial damage and confirmed by Cardiology.
Mortality
时间窗: up to 6 months following SCD treatment initiation
Death
Percentage of subjects with reversal of WRF and increase eGFR and PCW
时间窗: up to 6 days after initiation of SCD therapy
Among patients with WRF, the percentage of subjects with reversal of WRF (≥ 0.5 mg/dL reduction of serum creatinine from level at study entry), and achieving an eGFR \> 30 ml/min/1.73 m2 and PCWP at or below level at study entry at termination of SCD therapy.
Percentage of subjects who no longer have severe right ventricular failure
时间窗: up to 6 days after initiation of SCD therapy
Among subjects with severe RVF, the percentage of subjects who no longer have severe right ventricular failure, as evidenced by absence of 3 or more of the following 4 indicators of right ventricular failure: 1. CVP \> 16 mmHg 2. CVP/PCWP \> 0.65 3. RVSWI \< 300 mmHg \* mL/m 4. PAPi \< 2
次要结局
- Percentage of subject receiving a left ventricular assist device(up to 30 days after the last SCD)
- Change in 24 hour urine volume(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in urine sodium(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in urine creatinine(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in urine urea(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in creatinine clearance(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in urine urea clearance(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in Pulmonary Capillary Wedge Pressure (PCWP)(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in serum sodium(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in serum potassium(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in serum dissolved carbon dioxide (CO2)(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in blood urea nitrogen (BUN)(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Change in serum creatinine(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Percentage of subjects with reduction of serum creatinine (≥ 0.5 mg/dL) and PCWP (≤ 18 mmHg)(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)
- Percentage of subjects receiving a left ventricular assist device with serum creatinine ≥ 0.5 mg/dL below level at study entry(30 days following discontinuation of SCD)
- Change in right ventricular fractional area change(change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation)