Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist Oral Anticoagulants (NOAC) With Tranexamic Acid
Brief Summary: Novel, non-vitamin K antagonist oral anticoagulants (NOAC) target selected players in the coagulation cascade as the direct thrombin inhibitor dabigatran and the factor Xa-inhibitors apixaban and rivaroxaban. Intracerebral hemorrhage (ICH) is the most feared complication of NOAC treatment (NOAC-ICH).

Outcome of NOAC-ICH can be devastating and is a major cause of death and disability. There is no proven treatment for NOAC-ICH. Hematoma expansion (HE) is associated with unfavorable outcome. Tranexamic acid (TA) is an anti-fibrinolytic drug that is used in a number of bleeding conditions other than ICH.


Options:
A: 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.
B: 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
C: Inclusion Criteria:

* Acute, spontaneous ICH (including bleeding in cerebellum) diagnosed by non-enhanced CT scan within five hours of symptom onset. (Time of onset is defined as the last time the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep)
* Age \>/= 18 years through 80 years (candidates must have had their 18th birthday, but not had their 81st birthday)
* For spot positive patients, dosing of study drug within 90 minutes of enrolling CT scan

Exclusion Criteria:

* Time of symptom onset of ICH is unknown or more than five hours prior to baseline CT scan,
* ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, thrombolytic treatment of any condition (e.g., myocardial infarction, cerebral infarction, etc.), central nervous system (CNS) tumor or CNS infection
* Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
* Serum creatinine \> 1.4 mg/dl (123 μmol/L). Sites that currently perform CTA as standard of care for ICH will follow their standard procedures regarding renal insufficiency.
* Known allergy to iodinated contrast media
* Intravenous or intra-arterial administration of iodinated contrast media within the previous 24 hours of baseline CT scan
* Known hereditary (e.g., hemophilia) or acquired hemorrhagic diathesis, coagulation factor deficiency, or anticoagulant therapy with international normalized ration (INR) \> 1.2
* Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl)
* Unfractionated heparin use with abnormal partial thromboplastin time (PTT)
* Low-molecular weight heparin use within the previous 24 hours
* GPIIb/IIIa antagonist use in the previous two weeks
* Direct thrombin inhibitor or factor Xa inhibitor within the previous 48 hours
* Glasgow Coma Scale score \< 8 at time of proposed enrollment
* Pre-admission modified Rankin Scale score \> 2
* Baseline ICH volume of \< 0.5 cc (Hematoma volume will be estimated by local investigators from the baseline CT using the "ABC / 2 method".)
* Baseline ICH volume of \> 90 cc
* Planned surgical evacuation of ICH within 24 hours of symptom onset (placement of intraventricular catheter is not a contraindication to study enrollment.)
* Evidence of acute or subacute ischemic stroke on baseline qualifying CT scan
* Clinical history of thromboembolism or ischemic vascular disease, including myocardial infarction, coronary artery bypass surgery, cardiac angina, transient ischemic attack, ischemic stroke, peripheral artery disease (vascular claudication), cerebral bypass surgery, carotid endarterectomy, deep venous thrombosis, pulmonary embolism, or coronary or cerebrovascular angioplasty or stenting. (Clinically silent evidence of old ischemia on EKG (Q waves) or CT scan (silent old infarct) will not be considered reasons for exclusion.)
* Baseline electrocardiogram shows evidence of acute cardiac ischemia (ST elevation in two contiguous leads, new left bundle branch block (LBBB), or ST depression)
* Clinical history suggestive of acute cardiac ischemia (e.g., chest pain)
* Abnormal baseline troponin
* Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission
* Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
* 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 the time of STOP-IT enrollment
* Planned withdrawal of care or comfort care measures
* Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency or psychological disorder)
* Informed consent cannot be obtained from the patient or legally authorized representative
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: D