Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial

Intracerebral Hemorrhage Clinical Trial

— FASTEST  

Official title:

Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03496883
• Other study ID #: UCincinnatifastest
• Secondary ID: 1U01NS110772-012
• Status: Recruiting
• Phase: Phase 3
• Start date: December 3, 2021
• Est. completion date: January 1, 2028

Study information

• Verified date: June 2024
• Source: University of Cincinnati
• Contact: Joseph Broderick, MD
• Phone: (513) 919-5404
• Email: joseph.broderick[@]uc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 860
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Hemorrhagic Stroke
• Intracerebral Hemorrhage

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	University of Calgary - Foothills Medical Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	University of Montreal Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	St. Michaels Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Germany	University Hospital Augsburg	Augsburg
Germany	Charite University Medicine Berlin	Berlin
Germany	Clinic Frankfurt Hoechst	Frankfurt	Hessen
Germany	University Hospital Heidelberg	Heidelberg	Baden-Württemberg
Germany	University Hospital Tuebingen	Tuebingen
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	National Cerebral and Cardiovascular Center	Suita	Osaka
Japan	Kyorin University Hospital	Tokyo
Japan	Toranomon Hospital	Tokyo
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Santa Creu and Sant Pau Hospital	Barcelona	Catalonia
Spain	Girona University Hospital	Girona	Catalonia
Spain	Vall d'Hebron University Hospital (VHUH)	Horta	Barcelona
Spain	Bellvitge University Hospital,	L'Hospitalet de Llobregat	Barcelona
Spain	Arnau de Vilanova University Hospital	Lleida	Catalonia
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Queens Medical Centre	Nottingham
United Kingdom	John Radcliffe Hospital	Oxford	Oxfordshire
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent	Staffordshire
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mills Peninsula Medical Center	Burlingame	California
United States	M Health Fairview Ridges Hospital,	Burnsville	Minnesota
United States	Medical University of South Carolina University Hospital	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
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	Henry Ford Hospital	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	M Health Fairview Southdale Hospital	Edina	Minnesota
United States	Kaiser Permanente Fontana Medical Center	Fontana	California
United States	UF Health Shands Hospital	Gainesville	Florida
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	Memorial Hermann Memorial City Medical Center	Houston	Texas
United States	Memorial Hermann-Texas Medical Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
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	North Shore University Hospital	Manhasset	New York
United States	M Health Fairview St. John's Hospital	Maplewood	Minnesota
United States	WellStar Kennestone Hospital	Marietta	Georgia
United States	M Health Fairview University of Minnesota Medical Center Hospital,	Minneapolis	Minnesota
United States	Mount Sinai West	New York	New York
United States	The Mount Sinai Hospital	New York	New York
United States	UC Irvine Medical Center,	Orange	California
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	VCU Medical Center	Richmond	Virginia
United States	Kaiser Permanente Riverside Medical Center	Riverside	California
United States	Mayo Clinic Saint Marys Campus	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	San Francisco General Hospital	San Francisco	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Toledo Hospital	Toledo	Ohio
United States	St. John Medical Center	Tulsa	Oklahoma
United States	Central DuPage Hospital	Winfield	Illinois
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Joseph Broderick, MD	National Institute of Neurological Disorders and Stroke (NINDS), Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Japan,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale (mRS)	Ordinal distribution with the following steps: 0-2, 3, 4-6	180 days
Secondary	mRS	Utility-weighted	180 days
Secondary	mRS	Score of 0-2	180 days
Secondary	EQ-5D	Quality of life scale	180 days
Secondary	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
Secondary	mRS	Ordinal distribution	90 days
Secondary	EQ-5D	Quality of life scale	90 days
Secondary	mRS	Ordinal distribution	180 days