Artikel
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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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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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.