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56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

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Clazosentan: a novel selective endothelin A receptor antagonist, prevents cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Clazosentan: ein neuer selektiver Endothelin A Rezeptor Antagonist, verhindert den zerebralen Vasospasmus nach aneurysmatischer Subarachnoidalblutung

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  • corresponding author P. Vajkoczy - Neurochirurgische Klinik, Universitätsklinikum Mannheim
  • B. Meyer - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • S. Weidauer - Institut für Neuroradiologie, Johann-Wolfgang-Goethe-Universität Frankfurt am Main
  • A. Raabe - Neurochirurgische Klinik, Johann-Wolfgang-Goethe Universität Frankfurt am Main
  • C. Thome - Neurochirurgische Klinik, Universitätsklinikum Mannheim
  • F. Ringel - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • V. Breu - Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
  • P. Schmiedek - Neurochirurgische Klinik, Universitätsklinikum Mannheim

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc11.05.-13.05

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0243.shtml

Published: May 4, 2005

© 2005 Vajkoczy et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

To investigate the safety and efficacy of the novel endothelin A (ETA) receptor antagonist clazosentan in patients with aneurysmal subarachnoid hemorrhage (SAH) following surgical aneurysm clipping.

Methods

The study consisted of two parts: a double-blind, randomized part A (clazosentan 0.2 mg/kg/h versus placebo starting within 48 h post SAH up to day 14) on which statistical inference was performed and an open-label Part B (clazosentan 0.4 mg/kg/h for 12 h followed by 0.2 mg/kg/h up to day 14 for patients with established angiographic vasospasm) that was for exploratory purposes only. The primary efficacy endpoint was the incidence/severity of angiographic vasospasm at day 8 after SAH.

Results

34 patients (Hunt and Hess grade 3-4, Fisher grade of 3 or higher) were recruited and 32 (15 clazosentan, 17 placebo) were retained in the Intent-To-Treat population; 19 patients entered part B. In part A, treatment with clazosentan resulted in a reduced incidence of angiographic cerebral vasospasm (40% vs 88%, p=0.008). Also, vasospasm severity was reduced in the clazosentan group (p=0.012). In part B, 50% of assessable patients initially treated with placebo demonstrated reversal of their angiographic vasospasm following initiation of clazosentan. The incidence of new infarctions in the clazosentan and placebo group was 15% and 44%, respectively (p=0.130). There was no adverse event pattern indicating a specific organ toxicity of clazosentan.

Conclusions

This study indicates that clazosentan reduces the frequency and severity of cerebral vasospasm following severe aneurysmal SAH with an incidence/severity of adverse events comparable to placebo.