Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial (FASTEST)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Biological: Recombinant Activated Factor VII (rFVIIa); Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary - Foothills Medical Centre
    • Edmonton, Alberta, Canada, AB T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michaels Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • University of Montreal Hospital
• Germany
  • Augsburg, Germany, 86156
    • University Hospital Augsburg
  • Berlin, Germany
    • Charité University Medicine Berlin
  • Tübingen, Germany, 72076
    • University Hospital Tuebingen
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • University Hospital Heidelberg
  • Hesse
    • Frankfurt am Main, Hesse, Germany
      • Clinic Frankfurt Hoechst
• Japan
  • Fukuoka, Japan
    • Kyushu Medical Center
  • Gifu, Japan
    • Gifu University Hospital
  • Kagoshima, Japan
    • Kagoshima City Hospital
  • Kobe, Japan
    • Kobe City Medical Center General Hospital
  • Kyoto, Japan
    • Japanese Red Cross Kyoto Daini Hospital
  • Morioka, Japan
    • Iwate Prefectural Central Hospital
  • Niigata, Japan
    • Niigata City General Hospital
  • Osaka, Japan
    • KMU University Hospital
  • Osaka, Japan
    • NHO Osaka National Hospital
  • Sapporo, Japan
    • Nakamura Memorial Hospital
  • Shimotsuke, Japan
    • Jichi Medical University Hospital
  • Tokyo, Japan
    • Kyorin University Hospital
  • Tokyo, Japan
    • Toranomon Hospital
  • Osaka
    • Suita, Osaka, Japan, 564-8565
      • National Cerebral and Cardiovascular Center
• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 21A 08916
      • Hospital Universitari Germans Trias i Pujol
    • Horta, Barcelona, Spain
      • Vall d'Hebron University Hospital (VHUH)
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Bellvitge University Hospital,
  • Catalonia
    • Barcelona, Catalonia, Spain, 08025
      • Santa Creu and Sant Pau Hospital
    • Girona, Catalonia, Spain, 17007
      • Girona University Hospital
    • Lleida, Catalonia, Spain, 25198
      • Arnau de Vilanova University Hospital
• United Kingdom
  • Newcastle upon Tyne, United Kingdom
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom
    • Queens Medical Centre
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • John Radcliffe Hospital
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • Royal Stoke University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente Baldwin Park Medical Center
    • Burlingame, California, United States, 94010
      • Mills Peninsula Medical Center
    • Downey, California, United States, 90242
      • Kaiser Permanente Downey Medical Center
    • Fontana, California, United States, 92335
      • Kaiser Permanente Fontana Medical Center
    • Harbor City, California, United States, 90710
      • Kaiser Permanente South Bay Medical Center
    • La Jolla, California, United States, 92037
      • UCSD Health La Jolla
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente West Los Angeles Medical Center
    • Orange, California, United States, 92868
      • UC Irvine Medical Center,
    • Riverside, California, United States, 92505
      • Kaiser Permanente Riverside Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92103
      • UCSD Medical Center - Hillcrest Hospital
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health Shands Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • The Queen's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Winfield, Illinois, United States, 60190
      • Central DuPage Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48208
      • Henry Ford Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • M Health Fairview Ridges Hospital,
    • Edina, Minnesota, United States, 55435
      • M Health Fairview Southdale Hospital
    • Maplewood, Minnesota, United States, 55109
      • M Health Fairview St. John's Hospital
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center Hospital,
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Saint Marys Campus
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10019
      • Mount Sinai West
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • OSU Wexner Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • St. John Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina University Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
  • Texas
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
    • Houston, Texas, United States, 77030
      • Memorial Hermann-Texas Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Healthcare
  • Virginia
    • Richmond, Virginia, United States, 23219
      • VCU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS)	Ordinal distribution with the following steps: 0-2, 3, 4-6	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS	Utility-weighted	180 days
mRS	Score of 0-2	180 days
EQ-5D	Quality of life scale	180 days
Change in the volume of ICH and ICH+IVH	As measured by non-contrast CT of the head	Between baseline CT and 24-hour CT
mRS	Ordinal distribution	90 days
EQ-5D	Quality of life scale	90 days
mRS	Ordinal distribution	180 days

Collaborators and Investigators

• Sponsor: Joseph Broderick, MD
• Collaborators: Novo Nordisk A/S; National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Joseph Broderick, MD, University of Cincinnati

Publications and helpful links

General Publications

• Naidech AM, Grotta J, Elm J, Janis S, Dowlatshahi D, Toyoda K, Steiner T, Mayer SA, Khanolkar P, Denlinger J, Audebert HJ, Molina C, Khatri P, Sprigg N, Vagal A, Broderick JP. Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial. Int J Stroke. 2022 Aug;17(7):806-809. doi: 10.1177/17474930211042700. Epub 2021 Sep 5.
• Yu W, Alexander MJ. Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design. Chin Med J (Engl). 2024 Dec 20;137(24):2899-2906. doi: 10.1097/CM9.0000000000003408. Epub 2024 Dec 10. No abstract available.
• Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: April 5, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Cerebral Hemorrhage; recombinant FVIIa
• Other Study ID Numbers: UCincinnatifastest; 1U01NS110772-01 (U.S. NIH Grant/Contract); 2019-003722-25 (EudraCT Number); U1111-1201-0087 (Other Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Results to be reported on ClinicalTrials.gov, and trial database prepared for NINDS for sharing with other investigators
• IPD Sharing Time Frame: Available 12 months after publication of primary results
• IPD Sharing Access Criteria: Approval by NINDS
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No