背景:创伤可能与严重危及生命的失血有关,这反过来可能会增加并发症和死亡的风险,特别是在没有适当治疗的情况下。羟乙基淀粉(HES)溶液用于容量疗法,以治疗因急性失血而导致的血容量不足,以维持或重新建立血液动力学稳定性,最终目标是避免器官灌注不足和心血管衰竭。当前的研究比较了6%HES130溶液(Volulyte6%)与电解质溶液(离子电解液)用于成人外伤患者的容量替代疗法,应欧洲药品管理局的要求,以更多地了解HES在创伤护理中的安全性和有效性。
方法:TETHYS是一种务实的,prospective,随机化,控制,双盲,多中心,多国试验在两个平行组进行.合格同意的成年人≥18岁,估计失血量≥500毫升,并且认为在钝性或穿透性创伤后24小时内需要进行初次手术,将随机接受个体化剂量的静脉注射治疗,其中6%HES130或电解质溶液,最长24小时或直到达到30ml/kg体重的最大日剂量,首先发生的任何事情。样本量估计为每组175名患者,总共350名患者(α=0.025单尾,功率1-β=0.8)。以探索性方式评估的复合主要终点将是90天死亡率和90天肾衰竭,定义为AKIN阶段≥2,RIFLE损伤/失效阶段,或在前3个月使用肾脏替代疗法(RRT)。次要疗效和安全性终点是液体给药和平衡,生命体征和血流动力学状态的变化,包括肾功能在内的实验室参数的变化,凝血,和炎症生物标志物,治疗期间不良事件的发生率,医院,和重症监护病房(ICU)的住院时间,适合ICU或出院,以及机械通气和/或RRT的持续时间。
结论:这项务实研究将增加6%HES130治疗创伤患者急性失血继发低血容量的安全性和有效性的证据。
背景:在EudraCT注册,不。:2016-002176-27(2017年4月21日)和ClinicalTrials.gov,ID:NCT03338218(2017年11月9日)。
BACKGROUND: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current
study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.
METHODS: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational
trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.
CONCLUSIONS: This pragmatic
study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.
BACKGROUND: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).