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

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ClinicalTrials.gov Identifier: NCT03496883
Recruitment Status : Not yet recruiting
First Posted : April 12, 2018
Last Update Posted : November 24, 2020
Sponsor:
Collaborators:
Novo Nordisk A/S
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Joseph Broderick, MD, University of Cincinnati

Study Description
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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.

Condition or disease Intervention/treatment Phase
Intracerebral Hemorrhage Biological: Recombinant Activated Factor VII (rFVIIa) Biological: Placebo Phase 3

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.

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 860 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Blinded study medication
Primary Purpose: Treatment
Official Title: Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Modified Rankin Scale (mRS) [ Time Frame: 180 days ]
    Ordinal distribution with the following steps: 0-2, 3, 4-6


Secondary Outcome Measures :
  1. mRS [ Time Frame: 180 days ]
    Utility-weighted

  2. mRS [ Time Frame: 180 days ]
    Score of 0-2

  3. EQ-5D [ Time Frame: 180 days ]
    Quality of life scale

  4. Change in the volume of ICH and ICH+IVH [ Time Frame: Between baseline CT and 24-hour CT ]
    As measured by non-contrast CT of the head

  5. mRS [ Time Frame: 90 days ]
    Ordinal distribution

  6. EQ-5D [ Time Frame: 90 days ]
    Quality of life scale

  7. mRS [ Time Frame: 180 days ]
    Ordinal distribution


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. IVH score > 7
  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. Low-molecular weight heparin use within the previous 24 hours
  13. Recent (within 90 days) carotid endarterectomy or coronary or cerebrovascular angioplasty or stenting
  14. Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
  15. 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
  16. Planned withdrawal of care or comfort care measures
  17. Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency, or psychological disorder)
  18. Known or suspected allergy to trial medication(s), excipients, or related products
  19. Contraindications to study medication
  20. Previous participation in this trial (previously randomized)
  21. Females of childbearing potential who are known to be pregnant or within 12 weeks post-partum and/or lactating at time of enrollment
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496883


Contacts
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Contact: Joseph Broderick, MD (513) 919-5404 joseph.broderick@uc.edu
Contact: James Grotta, MD (281) 387-2329 james.c.grotta@uth.tmc.edu

Sponsors and Collaborators
Joseph Broderick, MD
Novo Nordisk A/S
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Joseph Broderick, MD University of Cincinnati
More Information
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Responsible Party: Joseph Broderick, MD, Principal Investigator, University of Cincinnati
ClinicalTrials.gov Identifier: NCT03496883    
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 )
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: November 24, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results to be reported on ClinicalTrials.gov, and trial database prepared for NINDS for sharing with other investigators
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Available 12 months after publication of primary results
Access Criteria: Approval by NINDS

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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
Additional relevant MeSH terms:
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Cerebral Hemorrhage
Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
 Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases