Dysautonomia International

Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial

Purpose

The objective of the rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial is to establish the first treatment for acute spontaneous intracerebral hemorrhage (ICH) within a time window and subgroup of patients that is most likely to benefit. The central hypothesis is that rFVIIa, administered within 120 minutes from stroke onset with an identified subgroup of patients most likely to benefit, will improve outcomes at 180 days as measured by the Modified Rankin Score (mRS) and decrease ongoing bleeding as compared to standard therapy.

Condition

Intracerebral Hemorrhage

Eligibility

Eligible Ages: Between 18 Years and 80 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Patients aged 18-80 years, inclusive 2. Patients with spontaneous ICH 3. Able to treat with study medication (rFVIIa/placebo) within 120 minutes of stroke onset or last known well 4. Efforts to obtain informed consent per EFIC guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, U.K., Japan)

Exclusion Criteria

Score of 3 to 7 on the Glasgow Coma Scale 2. Secondary ICH related to known causes (e.g., trauma, aneurysm, arteriovenous malformation (AVM), oral anticoagulant use (vitamin K antagonists or novel oral anticoagulants) within the past 7 days, coagulopathy, etc.) 3. ICH volume < 2 cc or ≥ 60 cc 4. Blood filling 2/3 or more of one lateral ventricle of the brain, OR, blood filling at least 1/3 of both lateral ventricles. 5. Pre-existing disability (mRS > 2) 6. Symptomatic thrombotic or vaso-occlusive disease in past 90 days (e.g., cerebral infarction, myocardial infarction, pulmonary embolus, deep vein thrombosis, or unstable angina) 7. Clinical or EKG evidence of ST elevation consistent with acute myocardial ischemia 8. Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled) 9. Refusal to participate in study by patient, legal representative, or family member 10. Known or suspected thrombocytopenia (unless current platelet count documented above 50,000/μL) 11. Unfractionated heparin use with abnormal PTT 12. Pro-coagulant drugs within 24 hours prior to patient enrollment into the FASTEST trial (example, tranexamic acid or aminocaproic acid) 13. Low-molecular weight heparin use within the previous 24 hours 14. Recent (within 90 days) carotid endarterectomy or coronary or cerebrovascular angioplasty or stenting 15. Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered 16. Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until to the time of FASTEST enrollment 17. Planned withdrawal of care or comfort care measures 18. Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency, or psychological disorder) 19. Known or suspected allergy to trial medication(s), excipients, or related products 20. Contraindications to study medication 21. Previous participation in this trial (previously randomized) 22. Females of childbearing potential who are known to be pregnant or within 12 weeks post-partum and/or lactating at time of enrollment

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Blinded study medication

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator Recombinant Activated Factor VII (rFVIIa)	rFVIIa given as IV injection over 2 minutes within 120 minutes of stroke onset	Biological: Recombinant Activated Factor VII (rFVIIa) Participants will be randomized in a double-blinded fashion to rFVIIa 80 µg/kg dose (maximum 10 mg dose) or matching placebo. Participants in both arms will receive best standard therapy as per published AHA Guidelines for ICH, including a target systolic blood pressure of 140 mm Hg. Other names: NovoSeven NiaStase
Placebo Comparator Placebo	Matching placebo given as IV injection over 2 minutes within 120 minutes of stroke onset	Biological: Placebo Participants will be randomized in a double-blinded fashion to rFVIIa 80 µg/kg dose (maximum 10 mg dose) or matching placebo. Participants in both arms will receive best standard therapy as per published AHA Guidelines for ICH, including a target systolic blood pressure of 140 mm Hg.

Recruiting Locations

University of Alabama Hospital
Birmingham 4049979, Alabama 4829764 35233

Contact:
Elizabeth Liptrap, MD
elizabethle@uabmc.edu

St. Joseph's Hospital and Medical Center
Phoenix 5308655, Arizona 5551752 85013

Contact:
Supreet Kaur, MD
supreet.kaur@DignityHealth.org

Kaiser Permanente Baldwin Park Medical Center
Baldwin Park 5325866, California 5332921 91706