DOI: 10.1177/23969873231194123 ISSN:

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

Inez Koopman, Reinier WP Tack, Herman F Wunderink, Anke HW Bruns, Irene C van der Schaaf, Daniela Cianci, Kyra A Gelderman, Inge M van de Ridder, Elly M Hol, Gabriel JE Rinkel, Mervyn DI Vergouwen
  • Cardiology and Cardiovascular Medicine
  • Neurology (clinical)


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.


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,

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