Abstract 96: CompLement C5 Antibodies For Decreasing Brain Injury After Aneurysmal Subarachnoid Hemorrhage (CLASH): A Randomized Controlled Phase II Clinical Trial

Abstract

Introduction: The inflammatory response after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, and poor functional outcome. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. We investigated the pharmacodynamic efficacy and safety of eculizumab (a complement C5 antibody) in aSAH patients. Methods: We conducted a randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment in the Netherlands. Patients were randomized (1:1) to receive eculizumab plus standard care or to standard care alone. Eculizumab (1200 mg) was administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group received prophylactic antibiotics for 4 weeks and prophylactic antifungal therapy if the patient had a central line or an external ventricular shunt and a positive fungal or yeast culture. The primary outcome was C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes included the occurrence of adverse events, eculizumab concentration and inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aimed to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. Results: A total of 31 patients have been included, of which 26 with CSF samples. Conclusions: Final results will be presented at the conference. Trial registration: Netherlands Trial Register: NTR6752. European Clinical Trials Database (EudraCT): 2017-004307-51.