title: Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage.
abstract: Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.
authors.affiliation: Academic Neurosurgery Unit and Wolfson Brain Imaging Centre, University of Cambridge, UK. jdpsecretary@medschl.cam.ac.uk
authors.forename: J D
authors.initials: JD
authors.lastname: Pickard
authors.forename: P J
authors.initials: PJ
authors.lastname: Kirkpatrick
authors.forename: T
authors.initials: T
authors.lastname: Melsen
authors.forename: R B
authors.initials: RB
authors.lastname: Andreasen
authors.forename: L
authors.initials: L
authors.lastname: Gelling
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authors.initials: T
authors.lastname: Fryer
authors.forename: J
authors.initials: J
authors.lastname: Matthews
authors.forename: P
authors.initials: P
authors.lastname: Minhas
authors.forename: P J
authors.initials: PJ
authors.lastname: Hutchinson
authors.forename: D
authors.initials: D
authors.lastname: Menon
authors.forename: S P
authors.initials: SP
authors.lastname: Downey
authors.forename: I
authors.initials: I
authors.lastname: Kendall
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: T A
authors.initials: TA
authors.lastname: Carpenter
authors.forename: E
authors.initials: E
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: Persson
mesh_terms: D000328:Adult; D017542:Aneurysm, Ruptured; D015942:Factor VIIa / Q000008:administration & dosage*; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications*; D011994:Recombinant Proteins / Q000008:administration & dosage; D055502:Secondary Prevention; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D015942:Factor VIIa