E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Acute bleeding into the brain |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048863 |
E.1.2 | Term | Hemorrhagic stroke |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principal research question of the FASTEST trial is to establish the first treatment for acute spontaneous bleeding into the brain (acute haemorrhagic stroke, intracerebral haemorrhage (ICH)) within a time window and subgroup of patients that is most likely to benefit. The primary specific aim is to evaluate 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 daily activities (modified Rankin Scale (mRS)) at 180 days, as compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary research question of the FASTEST trial is to evaluate if treatment with rFVIIa within 2 hours of onset of spontaneous ICH decreases bleeding between routine baseline and 24 hour head imaging, as compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) 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) |
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E.4 | Principal 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 and ≥ 60 cc 4) IVH (intraventricular hemorrhage) score > 7 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 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 Rankin Focused Assessment Tool will be used to obtain mRS scores. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, at 30 Days, at 90 Days, at 180 Days |
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E.5.2 | Secondary end point(s) |
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. The primary safety measure of the study will be life-threatening thromboembolic complications during the first four days after completion of study drug. A significant life-threatening complication will be defined as development of: 1) acute myocardial infarction, 2) acute cerebral infarction, and 3) acute pulmonary embolism, defined as follows. Secondary measures of safety will include mortality at 180 days and mRS of 5-6 at 180 days. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
mRS at baseline, 30 days, 90 days and 180 days EQ-5D at 90 days and 180 days Change in volume of ICH and ICH-IVH at 24 hours Life-threatening thromboembolic complications during the first four days Mortality at 180 days |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Japan |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 30 |