Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial

Authors: Naidech, AM.; Grotta, J; Jordan E; Scott J; Dowlatshahi, D; Toyoda, K; Steiner, T; Mayer, SA.; Khanolkar, P; Denlinger, J; Audebert, HJ.; Molina, C; Khatri, P; Sprigg, N; Vagal, A; Broderick, JP.

Affiliations: Northwestern Medicine, Chicago, IL, USA. University of Texas at Houston, TX, USA. Medical University of South Carolina, Charleston, SC, USA. National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA. University of Ottawa, Ottawa, Canada. National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. New York Medical College, Valhalla, NY, USA. University of Cincinnati, OH, USA. Charité University Hospital, Berlin, Germany. Hospital Vall d’Hebron, Barcelona, Spain. University of Nottingham, Nottingham, UK.

Publication: International Journal of Stroke. September 2021

Abstract: INTRODUCTION: Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset. METHODS: Factor VIIa for Hemorrhagic 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 intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 μg/kg or placebo intravenously over 2 min. 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.