Abstract
Cerebral vasospasm is a common complication occurring after aneurysmal subarachnoid hemorrhage (SAH). It is recognized as a leading preventable cause of morbidity and mortality in this patient group, but its management is challenging, and new treatments are needed. Clazosentan is an endothelin receptor antagonist designed to prevent endothelin-mediated cerebral vasospasm. Vajkoczy et al. (Neurosurg 103:9–17, 2005) initially demonstrated that clazosentan reduced moderate/severe angiographically proven vasospasm by 55% relative to placebo. These findings led to the initiation of the CONSCIOUS trial program to further examine the efficacy and safety of clazosentan in reducing angiographic vasospasm and improving clinical outcome after aneurysmal SAH. In the first of these studies, CONSCIOUS-1, 413 patients were randomized to placebo or clazosentan 1, 5 or 15 mg/h. Clazosentan reduced angiographic vasospasm dose-dependently relative to placebo with a maximum risk reduction of 65% with the highest dose. Despite this, there was no benefit of clazosentan on the secondary protocol-defined morbidity/mortality endpoint; however, additional post-hoc and modified endpoint analyses provided some evidence for a potential clinical benefit. Two additional large-scale studies (CONSCIOUS-2 and CONSCIOUS-3) are now underway to further investigate the potential of clazosentan to improve long-term clinical outcome.
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Acknowledgments
The authors would like to thank Dr Jo Oswald and Dr Georgina Grell of Watermeadow Medical for medical writing and editorial assistance, which was supported by Actelion Pharmaceuticals Ltd. Dr Beck received travel support to attend ICCV 10 from Actelion Pharmaceuticals Ltd.
Conflict of Interest Statement We declare that we have no conflict of interest.
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Beck, J., Raabe, A. (2011). Clazosentan: Prevention of Cerebral Vasospasm and the Potential to Overcome Infarction. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/2. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0356-2_26
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DOI: https://doi.org/10.1007/978-3-7091-0356-2_26
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