Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients (LIBERAL-Trial)

围手术期贫血导致氧气供应受损，并有发生重要器官缺血的风险。在健康和健康的人中，贫血可以通过几种机制来补偿。然而，由于多种并存和与年龄相关的功能储备下降，老年患者的代偿机制较少。这项研究的目的是评估老年外科患者是否可以从自由红细胞(RBC)输血策略中受益，而不是限制性输血策略。自由试验是一项前瞻性、随机化、多中心、对照的临床第四阶段试验，随机选择2,470名接受中高风险非心脏手术的老年患者(≥70岁)。登记的患者只有在手术中或术后3天内血红蛋白(Hb)达到≤9g/dl时才会被随机分配到自由组(当Hb≤为9g/dl时输注单个红细胞单位，输血后Hb水平的目标范围为9-10.5g/dl)或限制组(当Hb≤为7.5g/dl时输注单个红细胞单位，输血后Hb水平的目标范围为7.5-9g/dl)。将对每个患者进行干预，直到出院或手术后最多30天，以最先发生的为准。主要疗效结果被定义为手术后90天内全因死亡率、急性心肌梗死、急性缺血性中风、急性肾损伤(III期)、急性肠系膜缺血和急性外周血管缺血的综合结果。关键的次要终点是输血患者的百分比、红细胞单位的数量、住院时间、在重症监护病房的住院时间、急性肾损伤I-II期、感染、再次住院、功能状态(Barthel指数)、与健康相关的生活质量以及具有90天和1年随访的综合因素。我们预计到第一个资助期(31.07.2022)结束时，我们将招募1625名患者(66%)。这项更新建议是必要的，以便我们能够继续招募，并将其余34%的患者随机分配。总之，自由试验将评估与手术后90天内的限制性输血策略相比，自由输血策略是否能减少老年人群非心脏手术后的主要不良事件的发生。试验注册：ClinicalTrials.gov(标识：NCT03369210)

Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2,470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤ 9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Key secondary endpoints are percentage of patients transfused, number of RBC units, length of stay in hospital, length of stay on intensive care unit, acute kidney injury stage I-II, infections, re-hospitalisation, functional status (Barthel index), health-related quality of life, and composite components with 90 days and 1 year follow-up. We expect that until end of the 1st funding period (31.07.2022), we will have recruited 1625 patients (66%). This renewal proposal is necessary in order to allow us to continue recruitment and to randomize the remaining 34% of patients. In conclusion, the LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. Trial registration: ClinicalTrials.gov (identifier: NCT03369210)