Safety and pharmacodynamic efficacy of eculizumab in aneurysmal subarachnoid hemorrhage (CLASH): A phase 2a randomized clinical trial.

Autor:	Koopman I; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Tack RW; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Wunderink HF; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Bruns AH; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., van der Schaaf IC; Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Cianci D; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Gelderman KA; Sanquin Diagnostic Services, Amsterdam, The Netherlands., van de Ridder IM; Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Hol EM; Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Rinkel GJ; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Vergouwen MD; Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Jazyk:	angličtina
Zdroj:	European stroke journal [Eur Stroke J] 2023 Dec; Vol. 8 (4), pp. 1097-1106. Date of Electronic Publication: 2023 Aug 22.
DOI:	10.1177/23969873231194123
Abstrakt:	Introduction: Complement C5 antibodies reduce brain injury after experimental subarachnoid hemorrhage. Patients and Methods: In this randomized, controlled, open-label, phase 2a clinical trial with blinded-outcome assessment, we included adult aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a tertiary referral center ⩽11 h after ictus. Patients were randomized (1:1) to eculizumab plus care as usual or to care as usual. Eculizumab (1200 mg) was administered <12 h, and on days 3 and 7 after ictus. In the intervention group, all patients received prophylactic antibiotics and, after a protocol amendment, fluconazole if indicated. Primary outcome was C5a concentration in cerebrospinal fluid (CSF) on day 3 after ictus. Safety was monitored during 4 weeks. In each group, 13 patients with CSF assessments were needed to detect a 55% reduction in CSF C5a concentration. Results: From October 2018 to May 2021, we enrolled 31 patients of whom 26 with CSF samples, 13 per group. Median C5a concentration in CSF on day 3 was 251 pg/ml [IQR: 103-402] in the intervention group and 371 pg/ml [IQR: 131-534] in the control group ( p  = 0.29). Infections occurred in two patients in the intervention group and four patients in the control group. One patient in the intervention group developed a C. albicans meningitis prior to the protocol amendment. Discussion and Conclusion: One dose of eculizumab did not result in a ⩾ 55% decrease in C5a concentration in CSF on day 3 after aSAH. The study did not reveal new safety concerns, except for a C. albicans drain-related infection prior to antifungal monitoring and treatment. Trial Registration: EudraCT 2017-004307-51, https://www.clinicaltrialsregister.eu/. Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
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