Intensive Care Medicine, Radboudumc, Nijmegen, The Netherlands
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
BMJ Open. 2023 Apr 3;13(4):e065613. doi: 10.1136/bmjopen-2022-065613.
Sepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings.
This is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with 'moderate to severe' chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial.
The trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal.
EudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results.
gov number: NCT04411472.
脓毒症是急性肾损伤（AKI）的主要病因，与高发病率和死亡率相关。碱性磷酸酶（ALP）是一种内源性解毒酶。在一项 2 期试验中，重组人 ALP 化合物伊洛福塔司（ilofotase alfa）未显示出安全性或耐受性问题。伊洛福塔司组在 28 天内肾功能改善的程度显著大于安慰剂组。此外，观察到 28 天全因死亡率的相对显著降低>40%。一项后续试验旨在证实这些发现。
这是一项全球、多中心、随机、双盲、安慰剂对照、序贯设计的 3 期试验，患者随机分配至安慰剂或 1.6mg/kg 伊洛福塔司组。随机分组按基线改良序贯器官衰竭评估（mSOFA）评分和试验地点分层。主要目的是通过证明脓毒症相关性 AKI 需升压治疗的患者 28 天全因死亡率降低来证实伊洛福塔司的生存获益。最多将在欧洲、北美、日本、澳大利亚和新西兰的 120 个左右的地点招募 1400 名患者。将进行最多 4 次中期分析。根据预设的决策规则，试验可能因无效或有效而提前终止。此外，还分析了患有 COVID-19 疾病和患有“中度至重度”慢性肾脏病的患者，每个队列各有 100 名患者。一个独立的数据监测委员会在整个试验期间的预定间隔评估安全性数据。
该试验获得了相关机构审查委员会/独立伦理委员会的批准，并按照《赫尔辛基宣言》的伦理原则、良好临床实践指南、《联邦法规》和所有其他适用法规进行。本研究的结果将决定伊洛福塔司在脓毒症相关性 AKI 的危重症患者中降低死亡率的潜力，并将在同行评议的科学期刊上发表。
EudraCT CT 编号 2019-0046265-24。美国 IND 编号 117 605 预结果。
gov 编号：NCT04411472。
