Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial
- Conditions
- Intracerebral Hemorrhage
- Interventions
- Biological: Recombinant Activated Factor VII (rFVIIa)Biological: Placebo
- Registration Number
- NCT03496883
- Lead Sponsor
- Joseph Broderick, MD
- Brief Summary
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.
- Detailed Description
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. Involving other countries may be possible in the future depending upon recruitment needs.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 860
- Patients aged 18-80 years, inclusive
- Patients with spontaneous ICH
- Able to treat with study medication (rFVIIa/placebo) within 120 minutes of stroke onset or last known well
- 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)
- Score of 3 to 7 on the Glasgow Coma Scale
- 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.)
- ICH volume < 2 cc or ≥ 60 cc
- Blood filling 2/3 or more of one lateral ventricle of the brain, OR, blood filling at least 1/3 of both lateral ventricles.
- Pre-existing disability (mRS > 2)
- Symptomatic thrombotic or vaso-occlusive disease in past 90 days (e.g., cerebral infarction, myocardial infarction, pulmonary embolus, deep vein thrombosis, or unstable angina)
- Clinical or EKG evidence of ST elevation consistent with acute myocardial ischemia
- Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
- Refusal to participate in study by patient, legal representative, or family member
- Known or suspected thrombocytopenia (unless current platelet count documented above 50,000/μL)
- Unfractionated heparin use with abnormal PTT
- Pro-coagulant drugs within 24 hours prior to patient enrollment into the FASTEST trial (example, tranexamic acid or aminocaproic acid)
- Low-molecular weight heparin use within the previous 24 hours
- Recent (within 90 days) carotid endarterectomy or coronary or cerebrovascular angioplasty or stenting
- Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
- 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
- Planned withdrawal of care or comfort care measures
- Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency, or psychological disorder)
- Known or suspected allergy to trial medication(s), excipients, or related products
- Contraindications to study medication
- Previous participation in this trial (previously randomized)
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Recombinant Activated Factor VII (rFVIIa) Recombinant Activated Factor VII (rFVIIa) rFVIIa given as IV injection over 2 minutes within 120 minutes of stroke onset Placebo Placebo Matching placebo given as IV injection over 2 minutes within 120 minutes of stroke onset
- Primary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) 180 days Ordinal distribution with the following steps: 0-2, 3, 4-6
- Secondary Outcome Measures
Name Time Method Change in the volume of ICH and ICH+IVH Between baseline CT and 24-hour CT As measured by non-contrast CT of the head
mRS 180 days Ordinal distribution
EQ-5D 90 days Quality of life scale
Trial Locations
- Locations (89)
University of Alabama Hospital
🇺🇸Birmingham, Alabama, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente Baldwin Park Medical Center
🇺🇸Baldwin Park, California, United States
Mills Peninsula Medical Center
🇺🇸Burlingame, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Kaiser Permanente Fontana Medical Center
🇺🇸Fontana, California, United States
Kaiser Permanente South Bay Medical Center
🇺🇸Harbor City, California, United States
UCSD Health La Jolla
🇺🇸La Jolla, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente West Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center,
🇺🇸Orange, California, United States
Kaiser Permanente Riverside Medical Center
🇺🇸Riverside, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
UCSD Medical Center - Hillcrest Hospital
🇺🇸San Diego, California, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
WellStar Kennestone Hospital
🇺🇸Marietta, Georgia, United States
The Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
M Health Fairview Ridges Hospital,
🇺🇸Burnsville, Minnesota, United States
M Health Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
M Health Fairview St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
M Health Fairview University of Minnesota Medical Center Hospital,
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Saint Marys Campus
🇺🇸Rochester, Minnesota, United States
Regions Hospital
🇺🇸St Paul, Minnesota, United States
Barnes Jewish Hospital
🇺🇸St. Louis, Missouri, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Mount Sinai West
🇺🇸New York, New York, United States
The Mount Sinai Hospital
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
St. John Medical Center
🇺🇸Tulsa, Oklahoma, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina University Hospital
🇺🇸Charleston, South Carolina, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Memorial Hermann Memorial City Medical Center
🇺🇸Houston, Texas, United States
Memorial Hermann-Texas Medical Center
🇺🇸Houston, Texas, United States
University of Utah Healthcare
🇺🇸Salt Lake City, Utah, United States
VCU Medical Center
🇺🇸Richmond, Virginia, United States
University of Calgary - Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
St. Michaels Hospital
🇨🇦Toronto, Ontario, Canada
University of Montreal Hospital
🇨🇦Montreal, Quebec, Canada
University Hospital Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Clinic Frankfurt Hoechst
🇩🇪Frankfurt, Hessen, Germany
University Hospital Augsburg
🇩🇪Augsburg, Germany
Charite University Medicine Berlin
🇩🇪Berlin, Germany
University Hospital Tuebingen
🇩🇪Tuebingen, Germany
National Cerebral and Cardiovascular Center
🇯🇵Suita, Osaka, Japan
Kyushu Medical Center
🇯🇵Fukuoka, Japan
Gifu University Hospital
🇯🇵Gifu, Japan
Kagoshima City Hospital
🇯🇵Kagoshima, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Japan
Japanese Red Cross Kyoto Daini Hospital
🇯🇵Kyoto, Japan
Iwate Prefectural Central Hospital
🇯🇵Morioka, Japan
Niigata City General Hospital
🇯🇵Niigata, Japan
KMU University Hospital
🇯🇵Osaka, Japan
NHO Osaka National Hospital
🇯🇵Osaka, Japan
Nakamura Memorial Hospital
🇯🇵Sapporo, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Japan
Kyorin University Hospital
🇯🇵Tokyo, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Vall d'Hebron University Hospital (VHUH)
🇪🇸Horta, Barcelona, Spain
Bellvitge University Hospital,
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Santa Creu and Sant Pau Hospital
🇪🇸Barcelona, Catalonia, Spain
Girona University Hospital
🇪🇸Girona, Catalonia, Spain
Arnau de Vilanova University Hospital
🇪🇸Lleida, Catalonia, Spain
John Radcliffe Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Queens Medical Centre
🇬🇧Nottingham, United Kingdom