Safety and efficacy of clazosentan monotherapy in aneurysmal subarachnoid hemorrhage with intracerebral hematoma: A real-world analysis

Objective Evidence for clazosentan in aneurysmal subarachnoid hemorrhage (aSAH) complicated by intracerebral hematoma (ICH) remains limited. We evaluated outcomes of clazosentan monotherapy in patients with ICH and compared it with conventional fasudil-based therapy Methods This retrospective observational cohort study included consecutive aSAH patients treated at a single tertiary care center between April 2015 and August 2025. Two analyses were performed: (1) among patients receiving clazosentan monotherapy, outcomes were compared between those with and without ICH; (2) among patients with aSAH complicated by ICH, outcomes were compared between clazosentan monotherapy and conventional fasudil-based therapy. The primary endpoint was favorable functional outcome [modified Rankin Scale (mRS) 0–2] at 6 months. Multivariable logistic regression adjusted for age and World Federation of Neurosurgical Societies (WFNS) grade on admission was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Among 59 clazosentan-treated patients, 17 had ICH. Patients with ICH had higher WFNS grades and more often underwent initial hematoma evacuation or decompressive craniectomy. After adjustment for age and WFNS grade, ICH was not significantly associated with favorable 6-month outcome (mRS 0–2) (adjusted OR 0.478, 95% CI 0.129–1.767; P = 0.268); additional adjustment for modified Fisher grade yielded similar results. No significant associations were observed between ICH and secondary efficacy or safety outcomes, and no patient discontinued clazosentan because of hematoma expansion or worsening perihematomal edema. In the ICH cohort (clazosentan, n = 17; conventional therapy, n = 75), clazosentan was not significantly associated with favorable outcome (adjusted OR 2.295, 95% CI 0.681–7.741; P = 0.180), with similar estimates after adjustment for hematoma volume or modified Fisher grade. Conclusion Despite greater baseline severity, ICH was not significantly associated with worse functional outcomes during clazosentan monotherapy. These findings suggest that clazosentan may remain a viable prophylactic option in patients with aSAH complicated by ICH, although further validation in larger cohorts is warranted.