A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping

• Published in: Brain & spine Vol. 3; p. 102673
• Main Authors: Kerschbaumer, Johannes, Freyschlag, Christian Franz, Petr, Ondra, Adage, Tiziana, Breitenbach J, Joerg, Wessels, Lars, Wolf, Stefan, Hecht, Nils, Gempt, Jens, Wostrack, Maria, Gmeiner, Matthias, Gollwitzer, Maria, Stefanits, Harald, Bendszus M, Martin, Gruber, Andreas, Meyer, Bernhard, Vajkoczy, Peter, Thomé, Claudius
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2023; Elsevier
• Subjects: Aneurysm clipping; Aneurysmal subarachnoid hemorrhage; Cerebral vasospasm; Local delivery; Neurosurgery; Nicardipine; Local delivery; Aneurysm clipping; Cerebral vasospasm; Nicardipine; Aneurysmal subarachnoid hemorrhage
• ISSN: 2772-5294; 2772-5294
• DOI: 10.1016/j.bas.2023.102673

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. The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. 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. 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. 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. •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.