Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of Days Alive Free of Stage 2-3 AKI
研究概览
简要总结
Our overarching goal is to improve the outcomes of critically ill COVID-19 patients with or at risk for development of acute kidney injury (AKI). The objective of this study is to determine the role of a protocol to manage urine alkalization using a simple medication that has been used for a very long time, is safe, and without significant side-effects. We aim to determine the feasibility and safety of a urine alkalinization protocol for the prevention of AKI in patients testing positive for COVID-19.
详细描述
Emerging evidence suggests that acute kidney injury (AKI) secondary to COVID-19 (COV-AKI) might result from direct infection of renal tubule epithelial cells (RTEC). A variety of epithelial cells express the ACE2 receptor which contains the receptor-binding domain (RBD) used by SARS-CoV-1 and SARS-CoV-2 to enter the cells. While direct infection of RTEC has not yet been proven data from multiple laboratories show virus in the kidney. It is this direct viral involvement of the RTEC that this proposal seeks to address.
One relatively simple approach would be to perturb the ability of the RBD to bind to its cellular (hACE2) receptor. Changes in pH may cause each amino acid residue, in the RBD, to assume a slightly different 'microscopic' conformation-dependent pKa value. Urine pH is normally 5.5- 6.5 (not too dissimilar to alveolar fluid-6.4-6.86) and can be easily and safely manipulated. In fact, urine alkalinization protocols have been used for decades to reduce renal toxicity from various compounds (especially chemotherapy) and are recommended by US and European toxicology societies. Here, the strategy will be deployed not for ion trapping but to inhibit the virus from infecting RTEC. Alkalinizing the urine using IV sodium-bicarbonate solution to pH of 7.5 or more can be easily and safely achieved.
While severe AKI does not appear to be a major part of the SARS-CoV-2 syndrome for most patients, when severe AKI does occur, mortality is very high and preventing early AKI may reduce AKI severity as the disease progresses.
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
- •Confirmed COVID-19 positive
- •Admission to ICU or step-down unit
- •Age ≥ 18 years old
排除标准
- •Stage 3 AKI by KDIGO criteria
- •CKD stage 4-5
- •Contraindications to Na bicarbonate therapy (e.g. met. alkalosis, severe heart failure)
- •Urine pH > 7.0
研究组 & 干预措施
Standard of Care
Standard of Care treatment
干预措施: Standard of Care (Other)
Sodium Bicarbonate
Sodium bicarbonate 225 mEq (225 mL of an 8.4% solution) intravenously over 1 hour. Sodium bicarbonate 8.4% solution should not exceed 900 ml (4 boluses) in 24 hours.
干预措施: Sodium bicarbonate (Drug)
结局指标
主要结局
Number of Days Alive Free of Stage 2-3 AKI
时间窗: 28 days post-treatment
Primary efficacy outcome will be the number of days alive and free of stage 2-3 AKI (up to 28) in each group.
pH
时间窗: 10 days
Primary feasibility outcome will be the proportion of patients treated who achieve \>50% of urine measurements pH ≥= 7.2 over the duration of treatment.
次要结局
- Vent-Free(28 days)
- Stage 2-3 AKI(28 days)
- Hospital-Free(60 days post-index hospitalization)