Faculty of Medicine, University of Queensland, Herston, Queensland, Australia
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
BMJ Open. 2022 Dec 20;12(12):e068933. doi: 10.1136/bmjopen-2022-068933.
Cryopreservation at -80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries.
CLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change in clinical practice. Cost-effectiveness analyses will be incorporated into each study such that, should clinical non-inferiority compared with standard care be demonstrated, the hospitals in each country that would benefit most from changing to a cryopreserved platelet blood bank will be known.
CLIP-II was approved by the Austin Health Human Research Ethics Committee (HREC/54406/Austin-2019) and by the Australian Red Cross Lifeblood Ethics Committee (2019#23). CLIPNZ-II was approved by the New Zealand Southern Health and Disability Ethics Committee (21/STH/66). Eligible patients are approached for informed consent at least 1 day prior to surgery. There is no provision for consent provided by a substitute decision-maker. The results of the two trials will be submitted separately for publication in peer-reviewed journals.
NCT03991481 and ACTRN12621000271808.
在 -80°C 下用二甲基亚砜进行冷冻保存可将血小板的货架期从 7 天延长至 2 年。只有有限的比较试验数据支持冷冻保存血小板作为治疗外科出血的安全性和有效性。冷冻保存的血小板目前在大多数国家尚未注册用于民用。
CLIP-II 和 CLIPNZ-II 是两项协调、盲法、多中心、随机、对照的临床非劣效性试验，比较了冷冻保存血小板与传统液体血小板治疗心脏手术出血时的出血、输血、安全性和成本结果。CLIP-II 计划在澳大利亚的 12 家三级医院招募患者；CLIPNZ-II 将在新西兰的 5 家三级医院招募患者。除了冷冻血小板准备的细节外，这两项试验使用了几乎相同的方案。术前确定为需要输注血小板的高危患者，如果其主治医生认为需要输注血小板，则可输注多达 3 单位的研究血小板。主要终点是手术后重症监护病房（ICU）入住后 24 小时内通过手术引流的失血量。其他终点包括其他时间点的失血量、潜在并发症、不良反应、输血和液体需求、需要促凝治疗、术后抗凝剂开始使用的时间、血小板订单和输注开始之间的延迟、再次手术的需要、实验室和即时凝血指数、成本、机械通气时间、ICU 和住院时间以及死亡率。给 202 名（CLIP-II）或 228 名（CLIPNZ-II）接受研究血小板输注的患者输注血小板将提供 90%的效能，排除主要终点出现大于 20%劣效性的可能性。如果冷冻保存的血小板不比液体储存的血小板差，那么更长的保质期优势将证明临床实践的快速改变是合理的。成本效益分析将纳入每项研究中，以便在与标准护理相比显示出非劣效性的情况下，每个国家中从使用冷冻血小板血库中受益最多的医院将被确定。
CLIP-II 已获得奥斯汀健康人体伦理委员会（HREC/54406/Austin-2019）和澳大利亚红十字会生命血伦理委员会（2019#23）的批准。CLIPNZ-II 已获得新西兰南部健康和残疾伦理委员会的批准（21/STH/66）。至少在手术前一天向符合条件的患者提出知情同意。不允许替代决策者提供同意。两项试验的结果将分别提交给同行评议期刊发表。
NCT03991481 和 ACTRN12621000271808。
