Department of Neurology and Neurosurgery, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Bolognalaan 2-48, 3584 CJ, Utrecht, the Netherlands.
Trials. 2020 Nov 25;21(1):969. doi: 10.1186/s13063-020-04838-6.
The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve the outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH.
A randomised, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group.
The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH.
Netherlands Trial Register NTR6752 . Registered on 27 October 2017 European Clinical Trials Database (EudraCT) 2017-004307-51.
蛛网膜下腔出血（aSAH）后的炎症反应与早期脑损伤、迟发性脑缺血、不良功能预后和病死率有关。在实验性蛛网膜下腔出血研究中，SAH 后短时间内给予补体 C5 抗体可使脑损伤减少约 40%。补体成分 C5 可能是减少脑损伤、改善 aSAH 后预后的新治疗靶点。我们旨在研究依库珠单抗（补体 C5 抗体）在 aSAH 患者中的药效学疗效和安全性。
这是一项随机、对照、开放标签、盲法结局评估的 II 期临床试验。依库珠单抗（1200mg）在发病后<12 小时内静脉给药，在发病后第 3 天和第 7 天各给药 1 次。干预组患者接受 4 周预防性抗生素治疗，有中央导管或外部脑室引流管且真菌或酵母培养阳性的患者也接受 4 周预防性抗真菌治疗。主要结局是发病后第 3 天脑脊液（CSF）中 C5a 浓度。次要结局包括不良事件的发生、血液和 CSF 中的炎症参数、磁共振成像上的脑梗死以及临床和认知结局。我们旨在评估 26 例 CSF 评估患者，干预组 13 例，对照组 13 例。为了补偿早期病死率和无法获得 CSF，我们将每组纳入 20 例患者。
CLASH 试验是第一项研究依库珠单抗在 aSAH 早期阶段药效学疗效和安全性的试验。
荷兰试验注册库 NTR6752。于 2017 年 10 月 27 日注册 欧洲临床试验数据库（EudraCT）2017-004307-51。
