Safety and Efficacy Study of Etanercept for Aneurysmal Subarachnoid Hemorrhage

Summary

Subarachnoid hemorrhage (SAH) is a special type of stroke that typically results from a ruptured intracranial aneurysm, a weakening in the wall of a blood vessel. This type of life-threatening bleeding occurs in over 3000 Canadians per year, usually in working age adults. Although this type of stroke accounts for only 5-10% of strokes, it contributes a disproportionately larger percent of overall stroke morbidity and mortality due in part to the young age of those affected. If one is fortunate enough to survive the initial bleeding episode and the subsequent surgical treatment of the aneurysm, a patient may still develop secondary strokes 3 to 14 days after the initial bleed. These delayed strokes are the most significant cause of morbidity and mortality after SAH and may be potentially preventable. Currently, there is only one medication (an anti-hypertensive) that has convincingly shown to improve outcomes after SAH. The molecular pathway causing these delayed strokes is still not clear, and this is an active area of research. Animal studies have revealed that these delayed strokes may be caused by a pro-inflammation molecule called tumor necrosis factor alpha (TNFa). Delayed strokes were prevented experimentally by a TNFa blocker called etanercept. This clinical study, utilizing prophylactic treatment with etanercept in patients with SAH, will ensure the safety of this drug and determine its effectiveness in preventing delayed strokes.

Timeline

Start

2021-01

Primary completion

2022-01

Completion

2022-01

Publications

• Background Beeftink MM, Ruigrok YM, Rinkel GJ, van den Bergh WM. Relation of serum TNF-alpha and TNF-alpha genotype with delayed cerebral ischemia and outcome in subarachnoid hemorrhage. Neurocrit Care. 2011 Dec;15(3):405-9. doi: 10.1007/s12028-011-9556-1.
• Background Gruber A, Rossler K, Graninger W, Donner A, Illievich MU, Czech T. Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2000 Oct;12(4):297-306. doi: 10.1097/00008506-200010000-00001.
• Background Kerensky TA, Gottlieb AB, Yaniv S, Au SC. Etanercept: efficacy and safety for approved indications. Expert Opin Drug Saf. 2012 Jan;11(1):121-39. doi: 10.1517/14740338.2012.633509. Epub 2011 Nov 11.
• Background Vecchione C, Frati A, Di Pardo A, Cifelli G, Carnevale D, Gentile MT, Carangi R, Landolfi A, Carullo P, Bettarini U, Antenucci G, Mascio G, Busceti CL, Notte A, Maffei A, Cantore GP, Lembo G. Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage. Hypertension. 2009 Jul;54(1):150-6. doi: 10.1161/HYPERTENSIONAHA.108.128124. Epub 2009 May 26.
• Background Zhou QH, Sumbria R, Hui EK, Lu JZ, Boado RJ, Pardridge WM. Neuroprotection with a brain-penetrating biologic tumor necrosis factor inhibitor. J Pharmacol Exp Ther. 2011 Nov;339(2):618-23. doi: 10.1124/jpet.111.185876. Epub 2011 Aug 10.

Drugs

Indications