Multicenter Validation of a Unified Evidence-Based Treatment Protocol Focusing on Clazosentan for Managing Subarachnoid Hemorrhage

<b>Background/Objectives</b>: Effective management of aneurysmal subarachnoid hemorrhage (aSAH) requires an evidence-based treatment protocol. This study examines the outcomes of a unified, multicenter protocol emphasizing postoperative clazosentan as the first-line treatment for vasospasm. <b>Methods</b>: A standardized protocol prioritizing systemic management with clazosentan for vasospasm was implemented in April 2023. Cases treated between April 2022 and March 2024 were categorized into four groups: preprotocol fasudil treatment (PrF), preprotocol clazosentan treatment (PrC), postprotocol fasudil treatment (PoF), and postprotocol clazosentan treatment (PoC); these groups were analyzed. <b>Results</b>: Among 407 registered cases, 322 were eligible for analysis (PrF, 128; PrC, 69; PoF, 28; PoC, 97). PoC exhibited significantly lower angiographic vasospasm rates and had a lower incidence of symptomatic vasospasm compared with PrF (<i>p</i> = 0.048, <i>p</i> = 0.057). Logistic regression identified the clazosentan protocol as a predictive factor for vasospasm reduction (<i>p</i> = 0.02, OR 0.46 [0.22-0.94]; <i>p</i> = 0.022, OR 0.38 [0.16-0.91]). PoC experienced less fluid retention than the PrC (<i>p</i> < 0.001). Logistic regression confirmed protocol adherence with protocol reduced complications (<i>p</i> < 0.001, OR 0.24 [0.11-0.52]), included fluid retention (<i>p</i> < 0.001, OR 0.088 [0.03-0.29]). In older patients, no significant differences in vasospasm or complications were observed between PrF and PoC, but a trend toward reduced complications was observed in World Federation of Neurosurgical Societies (WFNS) grade V cases. <b>Conclusions</b>: Clazosentan-first protocol effectively reduces vasospasm and complications in aSAH management. It is also safe for older patients and those with WFNS grade V, offering a promising treatment strategy.