Denneman Nadine, Doorschodt Tom C, Coert Bert A, van den Berg René, Majoie Charles B L M, Müller Marcella C A, Middeldorp Saskia, Coppens Michiel, Kempeneers Marinus A, Tjerkstra Maud A, Labib Homeyra, Bandral Harssh Verdan, Baarse Martine, Platek Ewa E, Vandertop W Peter, Verbaan Dagmar, Post René
Neurosurgical Center Amsterdam, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
Neurovascular Disorders, Amsterdam Neuroscience, Amsterdam, The Netherlands.
BMJ Open. 2025 Aug 28;15(8):e096555. doi: 10.1136/bmjopen-2024-096555.
Aneurysmal subarachnoid haemorrhage (aSAH) is a severe condition associated with significant morbidity and case fatality rate. Delayed cerebral ischaemia (DCI) is a major factor contributing to poor outcomes. For long, DCI was thought to be caused by vasospasm, induced by blood in the subarachnoid space. Growing experimental and clinical evidence has shown an activation of the coagulation cascade and several other (intravascular) pathophysiological pathways, affecting the cerebral microcirculation. In a retrospective analysis of our aSAH patient registry, we observed lower in-hospital mortality and a significantly higher rate of discharge-to-home in patients treated with high-dose nadroparin, compared with patients treated with low-dose (prophylactic) nadroparin. This observation suggests a potential benefit of higher doses of nadroparin in the acute course after aSAH. We therefore hypothesise that treatment with high-dose nadroparin will improve clinical outcome in endovascularly treated patients with aSAH.
This is a single-centre, prospective, phase II randomised controlled trial. From January 2022, all eligible patients will be recruited. 100 patients will be randomised to the intervention arm, that is, nadroparin two times per day 5700 AxaIU, or the control arm, that is, nadroparin once daily 2850 AxaIU in patients with body weight ≤100 kg or once daily 5700 AxaIU in patients with body weight >100 kg, both for up to 21 days. The trial includes a 6-month follow-up period. The primary objective is 30-day mortality rate. Secondary outcomes include assessment of DCI, complications during admission, discharge location, clinical outcome (modified Rankin Scale), quality of life and total healthcare costs at 3 and 6 months follow-up.
Approval was obtained from the Medical Research Ethics Committee of the Amsterdam UMC, location Academic Medical Center (AMC) (MREC-number 2020_192), and recruitment has begun. The study results will be submitted for publication in peer-reviewed journals and presented at international conferences.
NCT04507178.
动脉瘤性蛛网膜下腔出血（aSAH）是一种严重疾病，具有较高的发病率和病死率。迟发性脑缺血（DCI）是导致不良预后的主要因素。长期以来，DCI被认为是由蛛网膜下腔血液诱导的血管痉挛所致。越来越多的实验和临床证据表明，凝血级联反应及其他几种（血管内）病理生理途径被激活，影响脑微循环。在对我们的aSAH患者登记处进行的回顾性分析中，我们观察到，与接受低剂量（预防性）那屈肝素治疗的患者相比，接受高剂量那屈肝素治疗的患者院内死亡率更低，出院回家率显著更高。这一观察结果提示高剂量那屈肝素在aSAH后的急性期可能具有益处。因此，我们假设高剂量那屈肝素治疗将改善接受血管内治疗的aSAH患者的临床结局。
这是一项单中心、前瞻性、II期随机对照试验。从2022年1月起，招募所有符合条件的患者。100例患者将被随机分配至干预组，即每日两次皮下注射那屈肝素5700抗Xa国际单位（AxaIU），或对照组，即体重≤100 kg的患者每日一次皮下注射那屈肝素2850 AxaIU，体重>100 kg的患者每日一次皮下注射那屈肝素5700 AxaIU，均持续21天。该试验包括6个月的随访期。主要目标是30天死亡率。次要结局包括DCI评估、住院期间的并发症、出院地点、临床结局（改良Rankin量表）、生活质量以及3个月和6个月随访时的总医疗费用。
已获得阿姆斯特丹大学医学中心学术医学中心（AMC）医学研究伦理委员会的批准（MREC编号：2020_192），且已开始招募患者。研究结果将提交至同行评审期刊发表，并在国际会议上展示。
NCT04507178。
