Please select the eligibility criteria that correspond to the clinical trial below.
Title: Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered At Earliest Time (FASTEST) Trial
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.


Options:
A: Inclusion Criteria:

* Spontaneous ICH (intraparenchymal), subdural hematoma (SDH) diagnosed by CT scanning ≤ 12 hours after onset of symptoms. In case of unknown time of symptom onset: time between last seen in healthy condition and first CCT ≤ 12 hours.
* Therapy receiving vitamin K antagonists (VKA)
* International Normalized Ratio (INR) ≥ 2
* Signed informed consent form, or signed informed consent by a legal representative, judicial consent in cases where no legal representative is available in time, or consent of an independent physician familiar with the indication in cases where the first three possibilities can not be realized.

Exclusion Criteria:

* Patients with ICH not related to vitamin-K antagonist therapy or
* Patients with secondary ICH related to infarction, hemophilia or other coagulopathy, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM) or severe trauma
* Deep Coma (GCS ≤ 5) at the time of admission or before intubation if intubated outside the hospital
* Known previous disability (mRS \> 2 before stroke occurred)
* Acute myocardial ischemia, acute septicemia, acute crush injury, any history of acute hemorrhagic disseminated intravascular coagulation, acute thrombotic stroke
* Known history of intermittent claudication
* Known recent thrombotic event \< 30 days
* Acute or known congestive heart failure (NYHA III, IV)
* Pulmonary edema
* Known liver failure (child-pugh-score C)
* Known alcohol or other drug abuse
* Known active malignant disease
* Known thrombocytopenia (platelets \<50,000/µL), hemorrhagic diathesis (primary defects of coagulation, fibrinolysis, platelets)
* History of hypersensitivity to the investigational products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
* Known allergy to heparin or history of heparin induced thrombocytopenia.
* Pregnancy and lactation
* Concomitant use of antithrombotic (with PTT \> 1.5 of normal PTT), thrombolytic treatment.
* Use of aspirin, clopidogrel or dipyridamole or combinations thereof (e.g. Aggrenox®) is not an exclusion criterion. These drugs should be discontinued and not restarted earlier than 24 hours after normalization of INR if indicated.
* Previous participation in this trial
B: 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
C: Inclusion Criteria:

* Patients presenting with an acute ICH
* Contrast extravasation within the haemorrhage, "spot sign", evaluated from the CTA according to three criteria, all of which must be present:

  1. Serpiginous or spot-like appearance within the margin of a parenchymal haematoma without connection to an outside vessel;
  2. The density (in Hounsfield units) should be greater than that of the background haematoma (site investigators are not required to document the density); and
  3. No hyperdensity at the corresponding location on non-contrast CT.
* Age ≥18 years
* Treatment can commence within 1 hour of initial CT and within 4.5 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well)
* Informed consent has been received in accordance to local ethics committee requirements

Exclusion Criteria:

* Glasgow coma scale (GCS) total score of \<8
* Brainstem ICH
* ICH volume \>70 ml as measured by the ABC/2 method
* ICH known or suspected by study investigator to be secondary to trauma, aneurysm, vascular malformation, haemorrhagic transformation of ischaemic stroke, cerebral venous thrombosis, thrombolytic therapy, tumor, or infection
* Contrast already administered within 24 hours prior to initial CT or contraindication to imaging with CT contrast agents (e.g. known or suspected iodine allergy or significant renal failure)
* Any history or current evidence suggestive of venous or arterial thrombotic events within the previous 12 months, including clinical, ECG, laboratory, or imaging findings. Clinically silent chance findings of old ischemia are not considered exclusion.
* Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency.
* Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral anticoagulation (e.g. warfarin, factor Xa inhibitor, thrombin inhibitor) within the previous 14 days, irrespective of laboratory values
* Pregnancy (women of childbearing potential must be tested)
* Planned surgery for ICH within 24 hours
* Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion)
* Participation in any investigational study in the last 30 days
* Known terminal illness or planned withdrawal of care or comfort care measures.
* Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
D: Inclusion Criteria:

* Acute intracerebral hemorrhage (symptom onset \<12h)
* Prior treatment with a novel direct oral anticoagulant (apixaban, dabigatran, edoxaban or rivaroxaban; last intake \<48hours or proven NOAC activity by relevant coagulation assays)
* Age \>18 years, No upper age limit
* Informed consent has been received in accordance to local ethics committee requirements

Exclusion Criteria:

* Severe pre-morbid disability (modified Rankin scale \>4)
* Anticoagulation with Vitamin K antagonists (VKA) (recent intake)
* Secondary intracerebral hemorrhage (e.g. arteriovenous malformation (AVM), tumor, trauma) Note it is not necessary for investigators to exclude underlying structural abnormality prior to enrolment, but where an underlying structural abnormality is already known, these patients should not be recruited.
* Glasgow coma scale \<5
* pregnancy
* Planned neurosurgical hematoma evacuation within 24 hours (before follow-up imaging)
* Pulmonary embolism/deep vein thrombosis within the last 2 weeks.

Answer: B