Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial

Clinical Trial

M Shibuya et al. J Neurosurg. 1992 Apr.

Abstract

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.

PubMed Disclaimer

Cited by

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis.
Zhou Y, Huang X, Hecker L, Kurundkar D, Kurundkar A, Liu H, Jin TH, Desai L, Bernard K, Thannickal VJ. Zhou Y, et al. J Clin Invest. 2013 Mar;123(3):1096-108. doi: 10.1172/JCI66700. Epub 2013 Feb 22. J Clin Invest. 2013. PMID: 23434591 Free PMC article.
Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase.
Hsiao ST, Spencer T, Boldock L, Prosseda SD, Xanthis I, Tovar-Lopez FJ, Van Beusekom HM, Khamis RY, Foin N, Bowden N, Hussain A, Rothman A, Ridger V, Halliday I, Perrault C, Gunn J, Evans PC. Hsiao ST, et al. Cardiovasc Res. 2016 Dec;112(3):689-701. doi: 10.1093/cvr/cvw210. Epub 2016 Sep 26. Cardiovasc Res. 2016. PMID: 27671802 Free PMC article.
Initial real-world experience of clazosentan for subarachnoid hemorrhage in Japan.
Maeda T, Okawara M, Osakabe M, Yamaguchi H, Maeda T, Kurita H. Maeda T, et al. World Neurosurg X. 2023 Dec 5;21:100253. doi: 10.1016/j.wnsx.2023.100253. eCollection 2024 Jan. World Neurosurg X. 2023. PMID: 38090191 Free PMC article.
Pleiotropic effects of statin therapy: molecular mechanisms and clinical results.
Wang CY, Liu PY, Liao JK. Wang CY, et al. Trends Mol Med. 2008 Jan;14(1):37-44. doi: 10.1016/j.molmed.2007.11.004. Trends Mol Med. 2008. PMID: 18068482 Free PMC article. Review.
Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage.
Liu GJ, Wang ZJ, Wang YF, Xu LL, Wang XL, Liu Y, Luo GJ, He GH, Zeng YJ. Liu GJ, et al. Eur J Clin Pharmacol. 2012 Feb;68(2):131-9. doi: 10.1007/s00228-011-1100-x. Epub 2011 Aug 12. Eur J Clin Pharmacol. 2012. PMID: 21837395

Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial - PubMed (original) (raw)