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Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use. Research question: The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. Material and methods: In this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment. Results: Ten patients across four dose groups were treated with NicaPlant® (3–13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm. Discussion and conclusion: The placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies. Editor highlights: • Post-hemmorrhagic vasospasm with neurological deterioration is one major concern in this disease. • Oral or intravenous nimodipine is standard of care after aSAH, but systemic side-effects often hinders adequate application. • Local delivery of spasmolytics during angiography is short lasting and has not proven a benefit in terms of outcome. • Local delivery over the critical period via prolonged released formulation may overcome the systemic side effects and have a beneficial effect in terms of outcome.