Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial

NCT ID: NCT03496883

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 860 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-03
• Study Completion Date: 2028-01-01

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.

Conditions

Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Recombinant Activated Factor VII (rFVIIa)

rFVIIa given as IV injection over 2 minutes within 120 minutes of stroke onset

Group Type: ACTIVE_COMPARATOR

Recombinant Activated Factor VII (rFVIIa)

Intervention Type: BIOLOGICAL

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.

Placebo

Matching placebo given as IV injection over 2 minutes within 120 minutes of stroke onset

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

NovoSeven; NiaStase

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Joseph Broderick, MD

OTHER

Sponsor Role: lead

Responsible Party

Joseph Broderick, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joseph Broderick, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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

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-Wurttemberg, Germany

Clinic Frankfurt Hoechst

Frankfurt am Main, Hesse, Germany

University Hospital Augsburg

Augsburg, , Germany

Charite University Medicine Berlin

Berlin, , Germany

University Hospital Tuebingen

Tübingen, , 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

Countries

United States; Canada; Germany; Japan; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39654449 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37870112 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34427473 (View on PubMed)

Related Links

https://www.nihstrokenet.org/trials/fastest/home

Related Info

Other Identifiers

1U01NS110772-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019-003722-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1201-0087

Identifier Type: OTHER

Identifier Source: secondary_id

UCincinnatifastest

Identifier Type: -

Identifier Source: org_study_id