Evaluating the Clinical Effectiveness of Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury (ESCALATE)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 660
- 试验地点
- 1
- 主要终点
- MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90)
研究概览
简要总结
The study investigates whether sodium bicarbonate is able to reduce the occurrence of major adverse kidney events on day 90 (MAKE90) in critically ill patients with metabolic acidosis and acute kidney injury (AKI). While its efficacy in this context has been suggested in a subgroup analysis of the BICAR-ICU trial it has not been confirmed in a double-blinded randomized controlled trial to date.
详细描述
Each year > 200 000 adult patients are admitted to intensive-care units (ICUs) in Germany of which around half develop acute kidney injury (AKI). AKI markedly increases morbidity, mortality, ICU/hospital length of stay, and the risk of progression to chronic kidney disease.2-4 Metabolic acidosis significantly raises hospital mortality, the need for kidney-replacement therapy (KRT), and the incidence of major adverse kidney events within 30 days (MAKE30).5,6 When AKI and metabolic acidosis coexist, 90-day mortality ranges from 53 % to 59 % (vs 26 % for AKI alone).
Acidaemia depresses cardiovascular function through reduced myocardial contractility, impaired catecholamine responsiveness, hyperkalaemia, pulmonary vasoconstriction and arrhythmogenesis.7,8 Restoring extracellular pH is therefore biologically plausible as a strategy to improve organ perfusion and outcomes.
Sodium bicarbonate is the most widely used buffer in clinical practice, yet high-quality evidence for its benefit in AKI with metabolic acidosis is lacking. To date, despite numerous calls for appropriately designed studies, there have only been two RCTs primarily addressing the effects of sodium bicarbonate in critically ill patients with severe acidosis.1,9 Due to methodological limitations (open-label study design, selection bias, risk of confounding) and lack in generalizability, the question on using sodium bicarbonate in critically ill patients with AKI and metabolic acidosis cannot be answered with certainty.
The "Evaluating the clinical effectiveness of sodium bicarbonate for critically ill patients with metabolic acidosis and acute kidney injury" trial is a multicenter, double-blinded, randomized controlled trial. It is designed to determine whether treatment with intravenous 8.4% weight/volume (w/v) sodium bicarbonate is superior to placebo in terms of the composite endpoint major adverse kidney events (MAKE) at day 90 (composite of death from any cause, receipt of any KRT within the 90-day period, or persistent renal dysfunction (defined as a creatinine value ≥200% of the baseline value) at day 90) in critically ill patients with AKI (KDIGO stage 2 or 3) and metabolic acidosis. The findings of the ESCALATE trial are expected to have significant implications for clinical practice and patient outcomes, both in Germany and internationally, by providing high-quality evidence to guide the management of a critically ill population with high risk of mortality.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Adult ≥ 18 years
- •Critically ill patients (requiring treatment on an ICU or IMC)
- •Metabolic acidosis, defined as all of the following:
- •Arterial pH ≤7.25
- •PaCO2 < 6.5kPa (<49 mmHg)
- •Standard bicarbonate ≤20 mmol/L
- •Standard Base Excess <-2
- •AKI stage 2 or 3 of the KDIGO classification
- •Written informed consent of the patient or legal representative or authorized representative or emergency inclusion (according to Article 35 EU-Regulation 536/2014)
排除标准
- •Pregnant or breastfeeding patients
- •Respiratory acidosis (acute or chronic) [dynamic, and if corrected, patient may be reconsidered for the trial]
- •Patients on KRT, or KRT immediately indicated and treating clinician(s) unwilling to defer
- •Deemed unsuitable for KRT
- •High output stoma/ileostomy
- •Percutaneous biliary drainage
- •End stage kidney failure defined as documented eGFR <15ml/min/1.73m 2 prior to onset of this acute illness or end stage kidney disease (ESKD) on dialysis
- •Known renal tubular acidosis
- •Diabetic ketoacidosis
- •High anion gap acid poisoning (e.g. polyethylene glycol (PEG), aspirin, methanol)
- •Symptomatic hypocalcaemia (Ionized calcium <1.05 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- •Hypernatremia (plasma sodium >150 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- •Severe hypokalemia (potassium <3.0 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- •Death perceived as imminent
- •Known hypersensitivity to sodium bicarbonate or EDTA (Disodiumedetate)
- •Previously randomized into ESCALATE
研究组 & 干预措施
Sodium Bicarbonate
Experimental: Sodium Bicarbonate 8.4% w/v Intravenous infusion according to the treatment algorithm targeting a pH>7.30
干预措施: Sodium Bicarbonate 8.4% Solution for Injection (Drug)
Balanced crystalloid solution
Placebo: Balanced crystalloid solution Intravenous infusion according to the treatment algorithm targeting a pH>7.30
干预措施: Balanced crystalloid solution (Drug)
结局指标
主要结局
MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90)
时间窗: 90 days after randomization
Incidence of suspected unexpected serious adverse reactions (SUSARs)
时间窗: from randomization until the end of treatment phase (up to day 7 OR Discharge from the intensive care unit, whatever comes first
次要结局
- KRT-dependence on day 90(90 days after randomization)
- KRT-free days, defined as difference between number of days receiving KRT of any form between randomization and day 90 and number of days alive(90 days after randomization)
- 90-day all-cause mortality (%)(90 days after randomization)
- Elevation of the creatinine level to ≥200% of base value at day 90 (one measurement between day 80 and 120 after randomization)(80 - 120 days after randomization)
- Receipt of any form of KRT within the 90-day time period after randomization(90 days after randomization)
- KRT-free days, defined as difference between number of days receiving KRT of any form between randomization and day 90(90 days after randomization)