The Artificial Kidney Initiation in Kidney Injury 2 A Multi-Centre, Randomized, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 768
- 试验地点
- 45
- 主要终点
- number of RRT-free days
研究概览
简要总结
The timing of renal replacement therapy (RRT) in the context of severe acute kidney injury (AKI) is one the most debated issues in critical care medicine. The Artificial Kidney Initiation in Kidney Injury (AKIKI) was the first large prospective multicenter randomized trial published on this topic. This study (published in the New England Journal of Medicine, July 2017) showed no significant difference between an early and delayed RRT initiation strategy in term of mortality. Nearly 50% of patients escaped RRT in the delayed strategy and this strategy was associated with less catheter-related infections and faster renal function recovery. Two (serum urea concentration >40 mmol/l and oliguria/anuria for more than 72 hours) of the 5 criteria which mandated RRT in the delayed strategy are still open to debate since they have never been shown to put patient at danger. To go further into our investigation of RRT criteria, the investigators designed a study that would compare the "delayed strategy" used in AKIKI that can now be considered as "standard" with another in which RRT is delayed for a longer period in the absence of a life-threatening complication (such as hyperkalemia or severe overload pulmonary edema).
详细描述
The timing of renal replacement therapy (RRT) in the context of severe acute kidney injury (AKI) is one the most debated issues in critical care medicine. The Artificial Kidney Initiation in Kidney Injury (AKIKI) was the first large prospective multicenter randomized trial published on this topic. This study conducted by our team (published in the New England Journal of Medicine, July 2017) showed no significant difference between an early and delayed RRT initiation strategy in term of mortality. Nearly 50% of patients escaped RRT in the delayed strategy and this strategy was associated with less catheter-related infections and faster renal function recovery. Two (serum urea concentration >40 mmol/l and oliguria/anuria for more than 72 hours) of the 5 criteria which mandated RRT in the delayed strategy are still open to debate since they have never been shown to put patient at danger. To go further into our investigation of RRT criteria,the investigators designed a study that would compare the "delayed strategy" used in AKIKI that can now be considered as "standard" with another in which RRT is delayed for a longer period in the absence of a potentially severe complication (such as hyperkalemia or severe overload pulmonary edema).
The AKIKI 2 study will be a prospective, multicenter, open-label, two-arm randomized trial.
The study will involve 2 stages (an observational stage and a randomization stage) At any time during these two stages, the occurrence of a potentially severe condition defined below will mandate strong consideration for immediate RRT initiation unless a medical treatment can very rapidly resolve the situation.
Criteria that mandate strong consideration for RRT initiation at any time during the 2 stages of the study
- Serum potassium concentration >6 mmol/l
- Serum potassium concentration >5.5 mmol/l persisting despite medical treatment
- Arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 <35 mmHg) or in a context of mixed acidosis with a PaCO2 >50 mmHg without possibility of increasing alveolar ventilation
- Acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2>95% (oxygen saturation) or FiO2>50% (inspired oxygen fraction) under invasive or non-invasive mechanical ventilation
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
- •All of the following criteria must be fulfilled to be included in the observational study (first stage):
- •Adults (>18 years)
- •Hospitalized in a study ICU.
- •Evidence of acute kidney injury compatible with the diagnosis of acute tubular necrosis in a context of ischemic or toxic aggression and who receive (or received for the same episode) invasive mechanical ventilation and/or catecholamine infusion.
- •Acute kidney injury stage 3 of KDIGO classification defined by at least one of the following criteria: serum creatinine concentration of more than 4 mg/dl (354 µmol/liter) or greater than 3 times the baseline creatinine level, anuria (urine output of 100 ml/day or less) for more than 12 hours, oliguria (urine output below 0.3 ml/kg/h or below 500 ml/day) for more than 24 hours.
- •To be randomized (randomization stage), supplemental criteria must be fulfilled. These criteria can appear either immediately after inclusion in the observational stage, or during the follow-up of the patient in the observational stage, in the absence of any non-inclusion criteria (listed below) at the time of randomization:
- •Oliguria/anuria (urine output <0.3 ml/kg/h or <500 ml/day) for more than 72 hours or serum urea concentration comprised between 40 and 50 mmol/l.
- •Affiliation to a social security regime
排除标准
- •Severity criteria mandating immediate RRT initiation (Table 1)
- •Serum urea level > 50 mmol/l
- •Severe chronic renal failure (defined by a creatinine clearance < 30 ml/min)
- •Patients with inclusion criteria already present for more than 24 hours (to avoid delayed inclusions)
- •AKI caused by urinary tract obstruction or renal vessel obstruction or tumour lysis syndrome or thrombotic microangiopathy or acute glomerulopathy
- •Poisoning by a dialyzable agent
- •Child C liver cirrhosis
- •Cardiac arrest without awakening
- •Moribund state (patient likely to die within 24h)
- •Patient having already received RRT for the current episode of AKI
- •Renal transplant
- •Treatment limitation (withholding or withdrawal)
- •Previous inclusion in this study
- •Subject deprived of freedom, subject under a legal protective measure
- •Pregnant or breastfeeding woman
结局指标
主要结局
number of RRT-free days
时间窗: Day 28 after randomization
One point will be given for each calendar day during the measurement period (i.e. from the first day of randomization to day 28) that a patient was both alive and free of RRT, assuming the patient survives and remains free of RRT for at least 3 consecutive calendar days after RRT weaning, whatever the vital status at day 28. Zero value will be given for patients with RRT initiated the first day of randomization who died before RRT weaning or who remained under RRT until day 28. With this definition, RRT-free days may concern days without RRT both before RRT initiation (a situation encountered by definition in the " delayed strategy" arm) and after RRT weaning (for the two strategies).
次要结局
- Number of hemorrhages (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of thrombocytopenia (randomization stage)(Until ICU discharge or day 28 after randomization)
- Time between randomization and RRT initiation (randomization stage)(Until ICU discharge or day 28 after randomization)
- Time to RRT weaning (randomization stage)(Until ICU discharge or day 28 after randomization)
- Total cost of RRT-related consumables (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of hypothermia (randomization stage)(Until ICU discharge or day 28 after randomization)
- Number of dialysis catheter-free day (randomization stage)(Until ICU discharge or day 28 after randomization)
- Hydration status (randomization stage)(Until ICU discharge or day 28 after randomization)
- Nutritional status (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of cardiac rhythm disorders (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of pericarditis (randomization stage)(Until ICU discharge or day 28 after randomization)
- Time to renal function recovery (randomization stage)(Until ICU discharge or day 28 after randomization)
- Barthel ADL (activity of daily living) index (randomization stage)(Day 60 after randomization)
- Rate of thrombosis of a large venous axis (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of hypophosphatemia (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of unexpected cardiac arrest (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of hemothorax (randomization stage)(Until ICU discharge or day 28 after randomization)
- Number of RRT sessions (randomization stage)(Until ICU discharge or day 28 after randomization)
- Percentage of patients with a decisions to withhold or withdraw life support therapies (randomization stage)(Until ICU discharge or day 28 after randomization)
- Duration of hospital stay (observational and randomization stage)(Limited to 60 days after randomization)
- Ventilator free-days (observational and randomization stage)(Day 28 after inclusion)
- RRT indications (observational and randomization stage)(Day 28 after inclusion)
- Duration of RRT(Until ICU discharge or day 28 after randomization)
- Rate of hyperkalemia (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of hypernatremia (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of pneumothorax (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of air embolism (randomization stage)(Until ICU discharge or day 28 after randomization)
- Number of arterio-venous fistulae (randomization stage)(Until ICU discharge or day 28 after randomization)
- Percentage of patients receiving RRT at least once in the " delayed" RRT strategy arm (randomization stage)(Until ICU discharge or day 28 after randomization)
- Rate of catheter-related bloodstream infection (randomization stage)(Until ICU discharge or day 28 after randomization)
- Duration of ICU stay (observational and randomization stage)(Limited to 60 days after randomization)
- ICU mortality (observational and randomization stage)(Limited to 60 days after randomization)
- Day 60 mortality (observational and randomization stage)(Day 60 after inclusion)
- Hospital mortality (observational and randomization stage)(Limited to 60 days after randomization)
- RRT modalities (observational and randomization stage)(Day 28 after inclusion)
- Time to spontaneous decrease in creatinine(Until ICU discharge or day 28 after randomization)
- Time to renal function recovery (observational and randomization stage)(Until ICU discharge or day 28 after randomization)
- Day 28 mortality (observational and randomization stage)(Day 28 after inclusion)