Pickard JD. Kirkpatrick PJ. Melsen T. Andreasen RB. Gelling L. Fryer T. Matthews J. Minhas P. Hutchinson PJ. Menon D. Downey SP. Kendall I. Clark J. Carpenter TA. Williams E. Persson L., Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage. Blood Coagulation & Fibrinolysis. Blood Coagulation & Fibrinolysis. 11 Suppl 1:S117-20, 2000.
Rebleeding following aneurysmal subarachnoid hemorrhage is a major factor contributing to unfavorable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk) might increase the risk of cerebral ischemia 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 hemorrhage 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 ischemia 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.