Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Reversal of hepatorenal syndrome
研究概览
简要总结
Hepatorenal syndrome (HRS) is a disease in which patients with cirrhosis (end stage liver failure) develop secondary kidney injury and failure. The current treatment available in the United States is a combination of octreotide and midodrine, which are meant to decrease the release of those hormones and raise the blood pressure, respectively, which would increase blood flow to the kidneys. Angiotensin 2 (Ang2) is a new vasopressor drug that was approved by the FDA in December 2017 for patients with low blood pressure and has been shown to have similar effects to octreotide and midodrine.
This study will investigate whether Ang2 reverses HRS among patients admitted to the intensive care unit (ICU) at Ronald Reagan Medical Center. Our study population will be patients with HRS who are already or will be admitted to the ICU. HRS will be defined by new internationally accepted guidelines published by the International Club of Ascites. All patients who are consented will undergo an Ang2 response trial, where low-dose Ang2 will be administered for 4 hours to see how the patients respond. This will help us characterize the nature of the patients' kidney failure for later analysis. Patients will then be randomized into the control group or the study group. Patients in the control group will receive octreotide (a subcutaneous injection) and midodrine (an oral drug). Patients in the study group will continue receiving intravenous infusion of Ang2. Patients in both groups will also receive albumin, a protein found commonly in human blood. Treatment will continue in both groups for four days, until complete reversal of HRS, dialysis, or death.
Our primary outcome will be rate of reversal of HRS, defined as improvement in kidney function.
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
- •Patients in the ICU with HRS-AKI defined as
- •Acute kidney injury defined as an increase in serum creatinine (sCr) >=0.3 mg/dl or >=50% from baseline within 7 days
- •Presence of cirrhosis and ascites
- •Absence of other causes such as shock, nephrotoxic drugs, or other suspected causes of kidney injury.
- •Lack of response to diuretic withdrawal and albumin challenge of 1 g/kg of body weight
排除标准
- •Age <18 years
- •Current or anticipated (within 24 hours) need for renal replacement therapy (RRT)
- •Cr > 6 mg/dl
- •Renal transplantation status
- •Fractional Excretion of Sodium (FeNa) > 2%
- •Pregnancy
- •Recent Cerebrovascular Accident (CVA), Myocardial Infarction (MI), venous or arterial thrombosis (within last 3 months)
- •Known hypercoagulable state other than cirrhosis
- •Uncontrolled hypertension (SBP > 160)
- •Anticipated mortality within 72 hours
- •Inability to obtain consent.
研究组 & 干预措施
Midodrine/Octreotide
This arm will receive standard of care treatment of midodrine, octreotide, and albumin.
干预措施: Albumin solution (Drug)
Midodrine/Octreotide
This arm will receive standard of care treatment of midodrine, octreotide, and albumin.
干预措施: Midodrine (Drug)
Midodrine/Octreotide
This arm will receive standard of care treatment of midodrine, octreotide, and albumin.
干预措施: Octreotide (Drug)
Angiotensin 2
This arm will receive the experimental treatment of angiotensin 2 infusion and albumin.
干预措施: Angiotensin II (Drug)
Angiotensin 2
This arm will receive the experimental treatment of angiotensin 2 infusion and albumin.
干预措施: Albumin solution (Drug)
结局指标
主要结局
Reversal of hepatorenal syndrome
时间窗: 4 days
Partial or complete reversal of HRS. Serum creatinine will be measured daily and compared against the patient's baseline creatinine. Partial reversal is defined defined as improvement of at least one AKI stage as defined by International Club of Ascites Acute Kidney Injury (ICA-AKI) criteria Complete defined as improvement of serum creatinine to within 0.3 mg/dl of baseline value). ICA-AKI criteria: * Stage 1: increase in sCr ≥0.3 mg/dl (26.5 μmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baseline * Stage 2: increase in sCr \>2-fold to 3-fold from baseline * Stage 3: increase of sCr \>3-fold from baseline or sCr ≥4.0 mg/dl (353.6 μmol/L) with an acute increase ≥0.3 mg/dl (26.5 μmol/L) or initiation of renal replacement therapy Angeli P et al. J Hepatology 2015:62(968-974)
次要结局
- Relapse of hepatorenal syndrome(14 days)
- Need for renal replacement therapy(4 days)
- Mortality(28 days)
- Serum sodium(4 days)