EXPRESS: Recombinant Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST): Protocol for a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial

Introduction: Intracerebral hemhaemorrhage (ICH) is the deadliest form of stroke. HemHaematoma expansion (HE), growth of the hemhaematoma between the baseline computed tomography (CT) scan and a follow-up CT scan at 24±6 hours, predicts long-term disability or death. Recombinant Factor VIIa (rFVIIa) has reduced HE in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on HE and potential benefit when administered within two hours of symptom onset. Methods: Factor VIIa for HemHaemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ~100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute ICH within two hours of symptom onset confirmed by CT, a hemhaematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemhaemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 mcg/kg or placebo intravenously over 2 minutes. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g., myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries. Discussion: In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.