gms | German Medical Science

67th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Korean Neurosurgical Society (KNS)

German Society of Neurosurgery (DGNC)

12 - 15 June 2016, Frankfurt am Main

NEWTON – Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage

Meeting Abstract

  • Daniel Hänggi - Neurochirurgische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Germany
  • Nima Etminan - Neurochirurgische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Germany
  • Hans-Jakob Steiger - Neurochirurgische Klinik, Heinrich-Heine-Universität Düsseldorf, Germany
  • R. Loch Macdonald - St. Michael’s Hospital, Toronto, Canada

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMO.02.05

doi: 10.3205/16dgnc005, urn:nbn:de:0183-16dgnc0055

Published: June 8, 2016

© 2016 Hänggi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. EG-1962 is a sustained release microparticle formulation of nimodipine. We conducted a phase 1/2a multicenter, controlled, randomized, open label, dose escalation study to determine the maximum tolerated dose (MTD) and assess the safety, tolerability and pharmacokinetics of administration of a single intraventricular dose of EG-1962 in patients with aSAH.

Method: Subjects with a ruptured saccular aneurysm treated by neurosurgical clipping or endovascular coiling were randomized if they were World Federation of Neurological Surgeons grade 2 to 4 after aneurysm repair and had a ventricular catheter placed as part of standard of care. Patients were randomized to receive either EG-1962 or oral nimodipine within 60 hours of aSAH. Objectives were to determine the MTD and safety tolerability of intraventricular EG 1962. The secondary objective was to determine release and distribution by measuring plasma concentrations of nimodipine. Clinical outcome was determined at 90 days after aSAH using the extended Glasgow outcome scale (GOSE), modified Rankin scale, Montreal cognitive assessment, telephone interview of cognitive status and Barthel index.

Results: Favorable outcome on the GOSE (6-8) was achieved in 5 of 9 patients treated with 100, 6 of 9 with 200 and 7 of 9 with 400 mg EG-1092. Two of 9 patients in the oral nimodipine group had favorable outcome. One serious adverse event possibly related to EG-1962 had no clinical sequelae in a patient in the 400 mg cohort. 2 dose limiting toxicities (increased intracranial pressure) were without clinical sequelae in patients in the 400 and 800 mg cohorts. There was no EG-1962-related hypotension as compared to hypotension in 3 of 9 with oral nimodipine. Pharmacokinetics showed plasma nimodipine concentrations that were sustained for at least 21 days and that increased in a dose-dependent fashion with increasing doses of EG-1962.

Conclusions: Intraventricular administration of nimodipine microparticles (EG-1962) were safe, associated with sustained and dose-dependent nimodipine plasma concentrations and showed promise for improving clinical outcome after SAH.