Gaudry Stéphane, Hajage David, Schortgen Fréderique, Martin-Lefevre Laurent, Tubach Florence, Pons Bertrand, Boulet Eric, Boyer Alexandre, Lerolle Nicolas, Chevrel Guillaume, Carpentier Dorothée, Lautrette Alexandre, Bretagnol Anne, Mayaux Julien, Thirion Marina, Markowicz Philippe, Thomas Guillemette, Dellamonica Jean, Richecoeur Jack, Darmon Michael, de Prost Nicolas, Yonis Hodane, Megarbane Bruno, Loubières Yann, Blayau Clarisse, Maizel Julien, Zuber Benjamin, Nseir Saad, Bigé Naïke, Hoffmann Isabelle, Ricard Jean-Damien, Dreyfuss Didier
Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, 178 rue des Renouillers, F-92700, Colombes, France.
Université Paris Diderot, Sorbonne Paris Cité, ECEVE, UMRS 1123, F-75010, Paris, France.
Trials. 2015 Apr 17;16:170. doi: 10.1186/s13063-015-0718-x.
There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT.
METHODS/DESIGN: This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, 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% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all.
The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT.
ClinicalTrials.gov NCT01932190.
对于重症监护病房（ICU）中无短期危及生命的代谢异常的急性肾损伤（AKI）患者，目前尚无经过验证的肾脏替代治疗（RRT）时机策略。迄今为止，尚无足够样本量的前瞻性随机研究探讨过这一问题。因此，存在显著的实践异质性，可能使患者面临不必要的危险操作或RRT的不当延迟。
方法/设计：这是一项多中心、前瞻性、随机、开放标签平行组临床试验，比较两种RRT启动策略对接受静脉注射儿茶酚胺或有创机械通气且AKI分级为3期（KDIGO 2012）的危重症患者总体生存的影响。在“早期”策略中，立即启动RRT。在“延迟”策略中，密切监测临床和代谢状况，仅在出现以下一个或多个事件（严重标准）时启动RRT，包括：随机分组后少尿或无尿超过72小时、血清尿素浓度>40 mmol/l、血清钾浓度>6 mmol/l、经药物治疗后血清钾浓度>5.5 mmol/l仍持续存在、在单纯代谢性酸中毒（动脉血二氧化碳分压<35 mmHg）或伴有动脉血二氧化碳分压≥50 mmHg的混合性酸中毒且无法增加肺泡通气的情况下动脉血pH<7.15、尽管进行利尿治疗但因液体过载导致急性肺水肿，导致严重低氧血症，在有创或无创机械通气下需要氧流量>5 l/min以维持脉搏血氧饱和度>95%或吸入氧浓度>50%。主要结局指标是总体生存，从随机分组（D0）开始测量直至死亡，无论死因如何。每位患者的最短随访时间为60天。计划进行两次中期分析，对分组情况设盲。预计总共将有620名受试者。
AKIKI研究将是极少数根据RRT时机评估AKI分级为3期（KDIGO 2012）的危重症患者死亡率的大型随机对照试验之一。结果应有助于临床医生决定何时启动RRT。
ClinicalTrials.gov NCT01932190。
