Spironolactone Administration to Prevent Ischemic Kidney Injury in Critically Ill Cancer Patients
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Acute kidney injury by 0.3 creatinine elevation
研究概览
简要总结
Acute kidney injury frequently affects cancer patients. The main cause of acute kidney injury is ischemic damage caused by transient decrease in renal blood flow, followed by blood flow restoration and accompanying reperfusion injury (ischemia-reperfusion injury. Several studies, mainly in animal models have tried to establish spironolactone role on kidney injury induced by ischemia-reperfusion injury. It has been demonstrated in renal transplant recipients that the administration of spironolactone can prevent oxidative stress and is safe. The group of cancer patients with states capable of producing tissue hypoperfusion (hypovolemic shock, heart failure, major surgery, use of anesthetics) are at increased risk of developing acute renal ischemia-reperfusion injury.
The investigators hypothesis is that spironolactone may be useful in preventing acute renal injury when administered during the first six hour of renal ischemia-reperfusion insult.
The purpose of this study is to determine the utility of spironolactone administered after an ischemic renal insult (major surgery) to prevent acute kidney injury in critically cancer patients.
Investigators propose a pilot study, randomized, double blind, placebo controlled trial, approved by the local ethical committee, to compare the efficacy of spironolactone to prevent acute kidney injury in patients after major surgery. Investigators will include 12 patients in spironolactone group (25mg daily for three days) and 12 patients in placebo group.
详细描述
Acute kidney injury frequently affects cancer patients, with an estimated annual risk of 17.5% after cancer diagnosis. In critically ill cancer patients, acute kidney injury incidence varies between 12 to 49%, and between 9 and 32% need renal replacement therapy. In this last group of patients, acute kidney injury frequently occurs as part of multiple organic failure and is associated with a mortality rate of 53 to 93%, as well as an increment in costs and days of hospitalization.
The main cause of acute kidney injury is ischemic damage caused by transient decrease in renal blood flow, followed by blood flow restoration and accompanying reperfusion injury (ischemia-reperfusion injury.
The decrease on renal blood flow is followed by an increment of aldosterone, this hormone acts on epithelial cells through mineralocorticoid receptors in several tissues, including heart and kidneys. In kidneys, aldosterone promotes sodium absorption and potassium excretion.
The decrease in renal blood flow is a strong stimulus for aldosterone secretion. This hormone has non-genomic actions on smooth muscle cells and vascular endothelium, causing vasoconstriction, interleukin and oxygen reactive species generation, and beta-transforming growth factor (TGF BETA) mediated fibrosis, among others.
At renal level, it has been demonstrated that mineralocorticoid receptor blockade can prevent proteinuria and glomerulosclerosis development in animal models of chronic kidney disease. Moreover, in chronic kidney disease patients with proteinuria, spironolactone addition to angiotensin converting enzyme inhibitors (ACEI), reduces proteinuria in 42% without a higher risk of hyperkalemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients admitted to the ICU in the immediate postoperative period (first 24 hours) of major surgery, defined as involving general anesthesia, ventilation, opening of large cavities (cranial, thoracic, abdominal).
- •Patients with informed consent signed by them or their responsible relative.
- •Patients who are likely to survive at least 48 hours after admission to the ICU.
- •Patients who have measured "baseline" creatinine before UCI admission, in the last three months.
排除标准
- •Patients who have contraindications for enteral medications.
- •Patients who have acute kidney injury at the time of admission.
- •Patients on renal replacement therapy prior to ICU admission.
- •Patients with previous diagnosis of chronic kidney disease G3b stage.
- •Patients with plasma potassium greater than 5.1mEq/L.
- •Hypersensitivity to spironolactone.
- •Septic shock.
- •Obstructive uropathy.
- •Renal transplantation.
- •Postoperative period of nephrectomy.
- •Pregnancy.
- •Known adrenal insufficiency.
- •Patients requiring a higher dose of norepinephrine 0.1mcg/kg/min for more than an hour to maintain mean arterial pressure equal to or greater than 70mmHg even after receiving fluid resuscitation.
- •Patients requiring the administration of inhibitors of angiotensin-converting enzyme (ACE) for its management.
- •Patients requiring an increase of 25% or more of the dose of norepinephrine to maintain mean arterial pressure equal of greater than 70mmHg during follow up.
研究组 & 干预措施
Spironolactone
Spironolactone 25 mg PO daily for three days. During five days investigators will collect values of plasma creatinine, sodium, potassium, blood ureic nitrogen, vital signs and urinary output.
干预措施: Spironolactone (Drug)
Placebo
Placebo 25mg PO daily for three days During five days investigators will collect values of plasma creatinine, sodium, potassium, blood ureic nitrogen, vital signs and urinary output.
干预措施: Placebo (Drug)
结局指标
主要结局
Acute kidney injury by 0.3 creatinine elevation
时间窗: 48 hours
Elevation of creatinine to 0.3mg/dL above baseline in the last 48 hours
Acute kidney injury by 1.5 times creatinine elevation
时间窗: 48 hours
Elevation of baseline creatinine 1.5 times above baseline
Acute kidney injury by urinary output
时间窗: 48 hours
Decreased urine output less than 0.5ml/kg/hr over a period of 6 continuous hours somewhere during the first 48 hours monitoring, after admission to the intensive care unit
次要结局
- Hyperkalemia(Up to 5 days)
研究者
Dr. Bertha Cordova-Sanchez
MD
Instituto Nacional de Cancerologia de Mexico