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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cincinnati College Of Medicine

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Jul 2025 → ongoing

Decision date (initial)

2024-09-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NovoNordisk A/S, Denmark · National Institute of Neurological Disorders and Stroke (NINDS), USA

External identifiers

EU CT number

2024-517383-28-00

EudraCT number

2019-003722-25

ClinicalTrials.gov

NCT03496883

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

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.
Part 1: 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.
Part 2: The primary specific aim is to find out if treatment with recombinant Factor VIIa (rFVIIa) within 2 hours of onset of spontaneous ICH and a positive spot sign in routine baseline CTA or treated within 90 minutes with or without a positive spot sign, 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 90 days, as compared to placebo.

Secondary objectives 1

1. Part 1: The secondary objectives of the FASTEST trial is to find out if treatment with rFVIIa within 2 hours of onset of spontaneous ICH decreases bleeding between baseline and 24 hour routine head imaging, as compared to placebo. Part 2: To test the hypothesis that treatment with rFVIIa within 2 hours of onset in appropriately selected patients with spontaneous ICH and a positive spot sign on CTA or treated within 90 minutes of onset with or without a positive spot sign decreases bleeding between baseline and 24-hour head imaging, as compared to placebo.

Conditions and MedDRA coding

Acute haemorrhagic stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) Patients aged 18-80 years, inclusive 2) Patients with spontaneous ICH (intracerebral hemorrhage) 3) Able to treat with study medication (rFVIIa/placebo) within 2 hours of stroke onset or last known well 4) Positive spot sign on baseline CTA (Part 2 only) or able to be treated within 90 minutes with or without a positive spot sign. 5) 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, Australia, Finland)

Exclusion criteria 1

1. 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 ml or ≥ 60 ml 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part 1: The primary outcome measure is the following distribution of the ordinal mRS (modified Rankin Score) at 180 days: 0-2, 3, and 4-6. Part 2: The primary outcome measure is the following distribution of the ordinal mRS (modified Rankin Score) at 90 days: 0-2, 3, and 4-6.

Secondary endpoints 1

1. 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; the trichotomous endpoint at 180 days for Part 2;and change in the volume of ICH and ICH-IVH (intraventricular hemorrhage) between the baseline routine CT and 24- hour routine CT.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cincinnati College Of Medicine

Sponsor organisation

University Of Cincinnati College Of Medicine

Address

260 Stetson Street

City

Cincinnati

Postcode

45267-0525

Country

United States

Scientific contact point

Organisation

University Of Cincinnati College Of Medicine

Contact name

Joseph P. Broderick

Public contact point

Organisation

University Of Cincinnati College Of Medicine

Contact name

Joseph P. Broderick

Third parties 2

Locations

2 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications