Recombinant coagulation Factor VIIa administered at the earliest time for the treatment of stroke caused by bleeding in the brain - FASTEST Trial

Phase 3

Suspended

Conditions: Acute haemorrhagic stroke

Registration Number: 2024-517383-28-00

Lead Sponsor: University Of Cincinnati College Of Medicine

Brief Summary: The main objective of the FASTEST trial is to establish the first treatment for acute spontaneous bleeding into the brain (intracerebral hemorrhage (ICH) within a time window and subgroup of patients that is most likely to benefit.

The primary specific aim is to find out if treatment with recombinant Factor VIIa (rFVIIa) within 2 hours of onset of spontaneous ICH

improves functional outcome as measured by a commonly used scale for measuring the degree of disability or dependence in the daily activities

(modified Rankin Scale (mRS) at 180 days, as compared to 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.

Recruitment & Eligibility

Status: Temporarily halted

Sex: Not specified

Target Recruitment: 114

Inclusion Criteria

Patients aged 18-80 years, inclusive 2) Patients with spontaneous ICH (intracerebral hemorrhage) 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 (exception from Informed Consent) guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, U.K., Japan)

Exclusion Criteria

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 thrombo-embolic or vaso-occlusive disease in past 90 days (e.g., cerebral infarction, myocardial infarction, pulmonary embolus, deep vein thrombosis, or unstable angina) 7) Clinical findings or EKG evidence of ST segment 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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary outcome measure is the following distribution of the ordinal mRS (modified Rankin Score) at 180 days: 0-2, 3, and 4-6.		The primary outcome measure is the following distribution of the ordinal mRS (modified Rankin Score) at 180 days: 0-2, 3, and 4-6.

Secondary Outcome Measures

Name	Time	Method
Secondary Endpoints include the ordinal mRS (all seven steps)routine CT, utility-weighted Rankin Score, mRS of 0-2, and EQ-5D at 90 days and 180 days; and change in the volume of ICH and ICH-IVH (intraventricular hemorrhage) between the baseline routine CT and 24- hour routine CT.		Secondary Endpoints include the ordinal mRS (all seven steps)routine CT, utility-weighted Rankin Score, mRS of 0-2, and EQ-5D at 90 days and 180 days; and change in the volume of ICH and ICH-IVH (intraventricular hemorrhage) between the baseline routine CT and 24- hour routine CT.

Trial Locations

Locations (18): Universitaetsklinikum Erlangen AöR
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Erlangen, Germany
RKU Universitaets und Rehabilitationskliniken Ulm gGmbH
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Ulm, Germany
Klinikum Frankfurt Hoechst GmbH
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Frankfurt Am Main, Germany
Universitaetsklinikum Heidelberg AöR
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Heidelberg, Germany
University Medical Center Hamburg-Eppendorf
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Hamburg, Germany
Universitaetsklinikum Tuebingen AöR
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Tuebingen, Germany
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
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Dresden, Germany
Universitaetsklinikum Leipzig AöR
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Leipzig, Germany
Charite Universitaetsmedizin Berlin KöR
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Berlin, Germany
Universitaetsklinikum Augsburg
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Augsburg, Germany
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Universitaetsklinikum Erlangen AöR
🇩🇪Erlangen, Germany
Bernd Kallmünzer
Site contact
+4991318544634
bernd.kallmuenzer@uk-erlangen.de