Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist

Study Overview
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Brief Summary
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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.

Official Title
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Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist Oral Anticoagulants (NOAC) With Tranexamic Acid

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic acid
* Drug: Saline 0.9%


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid<br>Intravenous tranexamic acid: 1g loading dose given as 100 mls infusion over 10 minutes, followed by another 1g in 250 mls infused over 8 hours. | Drug: Tranexamic acid<br>* intravenous<br>* Other names: Cyklokapron;|
| Placebo Comparator: Placebo<br>Saline 0.9% given in identical dosage as experimental | Drug: Saline 0.9%<br>* intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematoma expansion | Change in ICH-volume between baseline CT and follow-up-CT at 24 ± 3 hours of 33% relative or 6ml absolute increase | up to 27 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale (mRS) 0-4 at month 3; |  | 3 months | 
| mRS 0-3 at month 3; |  | 3 months | 
| Categorical shift in mRS at month 3 |  | 3 months | 
| mortality due to any cause at month 3 |  | 3 months | 
| In-hospital mortality |  | baseline until discharge from hospital (stay at hospital lasts on an average of 10 days) | 
| Absolute ICH growth volume by 24 ± 3 hours, adjusted for baseline ICH volume |  | up to 27 hours | 
| Symptomatic HE defined as HE and additionally a neurological deterioration of NIHSS >4 points or Glasgow Coma Scale (GCS) >2 points |  | up to 27 hours | 
| number of major thromboembolic events (myocardial infarction, ischemic stroke, pulmonary embolism - safety endpoints) |  | 3 months | 
| number of neurosurgical interventions (including craniectomy, external ventricular drain (EVD), hematoma evacuation) |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tranexamic acid, NOAC, Direct Oral Anticoagulant (DOAC), Direct oral anticoagulants, Non-Vitamin K antagonist oral anticoagulants