FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: A randomized controlled trial

Abstract

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH.

Materials and methods: We will perform an open-label randomized controlled trial comparing the standard of care, i.e. EVD alone, to the experimental treatment, i.e. IVF. We plan to include 440 patients to be able to show a 10% increase in the rate of good functional outcomes in the EVD+IVF group compared to the EVD alone group (α=0.05 and β=0.8). To obtain such sample, a multicenter trial is required, and to date 17 research sites in France have agreed to participate.

Perspective: FIVHeMA would be the first phase III trial evaluating the relevance of IVF in aneurysmal SAH. If IVF is shown to be beneficial, then a new therapeutic tool will be available to improve the outcomes of aneurysmal SAH patients.

Keywords: Delayed cerebral ischemia; External ventricular drainage; Intracranial aneurysm; Intraventricular fibrinolysis; Subarachnoid hemorrhage; Tissue plasminogen activator.