CLINICAL TRIAL / NCT03496883
Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial
- Interventional
- Active
- NCT03496883
Contact Information
Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial
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.
The investigators will perform a global, Phase III, randomized, double-blind controlled trial
of rFVIIa plus best standard therapy vs. placebo and best standard therapy alone. The
investigators will include participants with a volume of ICH ≥ 2 and < 60 cc, no more than a
small volume of intraventricular hemorrhage (IVH) (IVH score ≤ 7), age ≥ 18 and ≤ 80, Glasgow
Coma Scale of ≥ 8, and treated within 120 minutes from stroke onset. To minimize
time-to-treatment, the study will use emergency research informed consent procedures
(including exception from informed consent (EFIC) in the United States) and mobile stroke
units (MSUs), with a goal of ½ of participants treated within 90 minutes, as accomplished in
the NINDS t-PA trials. The FASTEST Trial will include approximately 100 hospital sites and at
least 15 MSUs in the NINDS-funded StrokeNet and key global institutions with large volumes of
ICH patients and the ability to treat them within 120 minutes of stroke onset. Recruitment of
860 participants over 3½ years is planned. Countries participating in the trial include the
United States, Canada, Japan, Germany, Spain, and the United Kingdom.
Participants will be randomized in a double-blinded fashion to rFVIIa 80 µg/kg dose (maximum
10 mg dose) or 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.
The primary outcome (ordinal mRS with the following categories: 0-2, 3, and 4-6) will be
determined at 180 days, but participants will be followed by remote assessment at 30 days and
90 days. To measure growth of ICH, all participants will have a standard of care baseline
non-contrast CT of the head and a repeat scan at 24 hours. Centralized volumetric
measurements of ICH, IVH, and edema will be performed for both time points.
Novo Nordisk A/S will manufacture and supply rFVIIa as a research medication for use in the
FASTEST Trial. Novo Nordisk A/S will also manufacture and supply matching placebo that is
identical to rFVIIa in appearance and administration.
Gender
All
Age Group
18 Years to 80 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. 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:
1. 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
- Intracerebral Hemorrhage