Department of Neurosurgery, Clinical Neuroscience Center, Universitätsspital and University of Zurich, Zurich, Switzerland.
Division of Internal Medicine, Universitätsspital and University of Zurich, Zurich, Switzerland.
BMC Neurol. 2022 Jul 18;22(1):267. doi: 10.1186/s12883-022-02789-w.
Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI.
HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses.
We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH.
ClinicalTrials.gov Identifier NCT04998370 . Date of registration: August 10, 2021.
临床前研究为蛛网膜下腔出血（SAH）后脑脊液（CSF）中无细胞血红蛋白（CSF-Hb）与继发性脑损伤之间的病理生理联系提供了强有力的依据。在一项单中心前瞻性观察性临床研究中，基于外部脑室引流（EVD）的 CSF-Hb 被证明是监测 SAH-SBI 的有前途的生物标志物。HeMoVal 研究的主要目的是前瞻性验证 EVD 基础 CSF-Hb 与 SAH 后第 14 天内的 SAH-SBI 之间的关联。次要目标包括评估 EVD 基础 CSF-Hb 对 SAH-SBI 的鉴别能力，并确定 EVD 基础 CSF-Hb 毒性的临床相关范围。此外，还将评估腰椎引流（LD）基础 CSF-Hb 与 SAH-SBI 的相关性及其鉴别能力。
HeMoVal 是一项前瞻性国际多中心观察性队列研究。纳入患有蛛网膜下腔出血（SAH）的成年患者。所有 SAH 患者均纳入研究，但我们的目标是在 SAH 后第 14 天内纳入 250 例 EVD 患者。在研究纳入时评估流行病学和疾病特异性基线指标。对于 EVD 或 LD 患者，在 SAH 后第 14 天内的每天早上，抽取 2ml CSF，然后在下午评估患者的 SAH-SBI、合并干预和并发症。3 个月后进行临床随访。对于统计分析，将队列分为 EVD、LD 和全队列。主要分析将基于广义加性模型量化 EVD 基础 CSF-Hb 与 EVD 队列中 SAH-SBI 之间的关联强度。次要分析包括基于广义加性模型在 LD 队列中 LD 基础 CSF-Hb 与 SAH-SBI 之间的关联强度，以及基于接收者操作特征（ROC）分析 CSF-Hb 对 SAH-SBI 的鉴别能力。
我们假设这项研究将验证 CSF-Hb 作为监测 SAH-SBI 的生物标志物的价值。此外，这项研究的结果将为未来针对 SAH 后 CSF-Hb 毒性的研究确定干预阈值提供潜在依据。
ClinicalTrials.gov 标识符 NCT04998370。注册日期：2021 年 8 月 10 日。
