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Randomized Controlled Trial
. 2024 Oct 1;81(10):1060-1065.
doi: 10.1001/jamaneurol.2024.2564.

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial

Lars Wessels  1   2 , Stefan Wolf  1   2 , Tiziana Adage  3 , Jörg Breitenbach  3 , Claudius Thomé  4 , Johannes Kerschbaumer  4 , Martin Bendszus  5 , Matthias Gmeiner  6 , Andreas Gruber  6 , Dorothee Mielke  7   8 , Veit Rohde  7 , Maria Wostrack  9 , Bernard Meyer  9 , Jens Gempt  9   10 , Gerhard Bavinzski  11 , Dorian Hirschmann  11 , Peter Vajkoczy  1   2 , Nils Hecht  1   2
Affiliations
Randomized Controlled Trial

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial

Lars Wessels et al. JAMA Neurol. .

Abstract

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.

Objective: To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.

Design, setting, and participants: This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated.

Intervention: During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group).

Main outcome and measures: The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography.

Results: Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups.

Conclusions and relevance: These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted.

Trial registration: ClinicalTrials.gov Identifier: NCT04269408.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wessels reported receiving travel expenses from BIT Pharma during the conduct of the study. Dr Adage reported receiving grants from the Austria Wirtschaftsservice and Forschungsförderungsgesellschaft, Österreich outside the submitted work, and patent EP3716951 licensed to Gebro Pharma. Prof Breitenbach reported receiving grants from Forschungsförderungsgesellschaft, Österreich and the Austria Wirtschaftsservice during the conduct of the study and patents EP2485717 and EP3716951 licensed to Gebro Pharma. Prof Thomé reported receiving grants from BrainLab, Idorsia, Intrinsic Therapeutics, and Signus Medical and personal fees from BrainLab, DepuySnythes, Intrinsic Therapeutics, Medacta, Signus Medical, Stryker, and Zeiss outside the submitted work. Dr Bendszus reported receiving personal fees from NeuroScios Core Lab during the conduct of the study and grants from the European Union and Deutsche Forschungsgemeinschaft and personal fees from Novartis, Guerbet, Springer, Boehringer Ingelheim, and Seagen outside the submitted work. Prof Mielke reported receiving lecture fees from Medtronic outside the submitted work. Dr Vajkoczy reported receiving shares from BIT Pharma. Dr Hecht reported receiving personal fees from Baxter, Penumbra, and Aesculap outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Flow Diagram
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References

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