A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping
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 vas...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
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| Series: | Brain and Spine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S277252942300961X |
| _version_ | 1827591461082759168 |
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| author | Johannes Kerschbaumer Christian Franz Freyschlag Ondra Petr Tiziana Adage Joerg Breitenbach J Lars Wessels Stefan Wolf Nils Hecht Jens Gempt Maria Wostrack Matthias Gmeiner Maria Gollwitzer Harald Stefanits Martin Bendszus M Andreas Gruber Bernhard Meyer Peter Vajkoczy Claudius Thomé |
| author_facet | Johannes Kerschbaumer Christian Franz Freyschlag Ondra Petr Tiziana Adage Joerg Breitenbach J Lars Wessels Stefan Wolf Nils Hecht Jens Gempt Maria Wostrack Matthias Gmeiner Maria Gollwitzer Harald Stefanits Martin Bendszus M Andreas Gruber Bernhard Meyer Peter Vajkoczy Claudius Thomé |
| author_sort | Johannes Kerschbaumer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:33:02Z |
| format | Article |
| id | doaj.art-3f2200bead6242d3af265651da6e28a4 |
| institution | Directory Open Access Journal |
| issn | 2772-5294 |
| language | English |
| last_indexed | 2024-03-09T01:33:02Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain and Spine |
| spelling | doaj.art-3f2200bead6242d3af265651da6e28a42023-12-09T06:09:13ZengElsevierBrain and Spine2772-52942023-01-013102673A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clippingJohannes Kerschbaumer0Christian Franz Freyschlag1Ondra Petr2Tiziana Adage3Joerg Breitenbach J4Lars Wessels5Stefan Wolf6Nils Hecht7Jens Gempt8Maria Wostrack9Matthias Gmeiner10Maria Gollwitzer11Harald Stefanits12Martin Bendszus M13Andreas Gruber14Bernhard Meyer15Peter Vajkoczy16Claudius Thomé17Department of Neurosurgery, Medical University Innsbruck, Innsbruck, Austria; Corresponding author. Department of Neurosurgery, Medical University of Innsbruck Anichstrasse 35, 6020 Innsbruck, Austria.Department of Neurosurgery, Medical University Innsbruck, Innsbruck, AustriaDepartment of Neurosurgery, Medical University Innsbruck, Innsbruck, AustriaBIT Pharma GmbH, Graz, AustriaBIT Pharma GmbH, Graz, AustriaDepartment of Neurosurgery, Charité Berlin, Berlin, GermanyDepartment of Neurosurgery, Charité Berlin, Berlin, GermanyDepartment of Neurosurgery, Charité Berlin, Berlin, GermanyDepartment of Neurosurgery, Klinikum Rechts der Isar, School of Medicine, Technical University Munich, Munich, GermanyDepartment of Neurosurgery, Klinikum Rechts der Isar, School of Medicine, Technical University Munich, Munich, GermanyDepartment of Neurosurgery, Kepler University Hospital and Johannes Kepler University, Linz, AustriaDepartment of Neurosurgery, Kepler University Hospital and Johannes Kepler University, Linz, AustriaDepartment of Neurosurgery, Kepler University Hospital and Johannes Kepler University, Linz, AustriaDepartment of Neuroradiology, University of Heidelberg, Heidelberg, GermanyDepartment of Neurosurgery, Kepler University Hospital and Johannes Kepler University, Linz, AustriaDepartment of Neurosurgery, Klinikum Rechts der Isar, School of Medicine, Technical University Munich, Munich, GermanyBIT Pharma GmbH, Graz, AustriaDepartment of Neurosurgery, Medical University Innsbruck, Innsbruck, AustriaIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S277252942300961XAneurysm clippingAneurysmal subarachnoid hemorrhageCerebral vasospasmLocal deliveryNicardipine |
| spellingShingle | Johannes Kerschbaumer Christian Franz Freyschlag Ondra Petr Tiziana Adage Joerg Breitenbach J Lars Wessels Stefan Wolf Nils Hecht Jens Gempt Maria Wostrack Matthias Gmeiner Maria Gollwitzer Harald Stefanits Martin Bendszus M Andreas Gruber Bernhard Meyer Peter Vajkoczy Claudius Thomé A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping Brain and Spine Aneurysm clipping Aneurysmal subarachnoid hemorrhage Cerebral vasospasm Local delivery Nicardipine |
| title | A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| title_full | A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| title_fullStr | A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| title_full_unstemmed | A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| title_short | A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| title_sort | randomized single ascending dose safety tolerability and pharmacokinetics study of nicaplant r in aneurysmal subarachnoid hemorrhage patients undergoing clipping |
| topic | Aneurysm clipping Aneurysmal subarachnoid hemorrhage Cerebral vasospasm Local delivery Nicardipine |
| url | http://www.sciencedirect.com/science/article/pii/S277252942300961X |
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