Effectiveness of Intravenous Tranexamic Acid in Primary Cerebral Hemorrhage for Prevention of Hematoma Progression: Protocol for a Randomized, Double Blind Placebo-controlled Trial

Study Overview
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Brief Summary
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Intracerebral hemorrhage is increasingly becoming a major burden in the society because of significant morbidity as well as mortality. Hematoma volume at the time of presentation as well as hematoma expansion and re-bleed or ongoing bleed further deteriorates the patient making a poor prognosis, however at present no therapy targets this pathological process. Though clinical studies do report benefit of using tranexamic acid in spontaneous intracerebral hemorrhage by reducing hematoma expansion rate as well as decreasing ongoing bleed, large randomized controlled trials have not shown any convincing advantage owing to various limitations in their design and methods. However, they uniformly did not find any significant side effect with the use of tranexamic acid. The aim of this study is to test the hypothesis that intravenous tranexamic acid is superior to placebo by reducing hematoma expansion when given within 24 h of spontaneous intracerebral hemorrhage.

Detailed Description
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Patients and Methods: Data will be collected (after Nepal Health Research Council approval) for 1 year as patient gets admitted with Intracerebral haemorrhage. 160 spontaneous intracerebral haemorrhage patients presenting within 24 hours of ictus or last known well will be taken in the study. Outcomes of these patients will be calculated to establish a relationship between hematoma expansion, underlying pathology and outcome of the patients. Results: Primary outcome i.e. radiological improvement (CT scan): Difference between hematoma volume with perilesional edema from baseline and 48-hour post treatment scan, hematoma location, and new infarction. Secondary outcomes: Neurological impairment (National Institutes of Health Stroke Scale) at day 7, Outcome: Dependency (modified Ranking Scale), Cognition (Telephone Interview Cognition Score-Modified), and mood (Zung Depression Scale) at days 10 and 90 and 180. Similarly, costs: Length of stay in hospital, readmission, ability to return back to daily activities. Also, Safety endpoints recorded until day 90: Death (cause), venous thromboembolism confirmed by ultrasound, vascular occlusive events (stroke/transient ischemic attack/myocardial infarction/peripheral artery disease), seizures. Serious adverse events (AEs) in first seven days will be analyzed and calculated.

Official Title
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Effectiveness of Intravenous Tranexamic Acid in Primary Cerebral Hemorrhage for Prevention of Hematoma Progression: Protocol for a Randomized, Double Blind Placebo-controlled Trial

Conditions
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Cerebral Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic Acid 500 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients presenting to the emergency department with symptom of hemorrhagic stroke within 24 hours from onset of symptom or last seen well. Patient who had a follow up Exclusion Criteria: Glasgow coma scale <9 after resuscitation (as this can lead to biasness; requires surgery) Contraindication to tranexamic acid, Hemorrhagic stroke secondary to trauma, Hemorrhage was caused by coagulopathy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: tranexamic acid<br>Four 5ml solution of either tranexamic acid 500mg or sodium chloride 0.9% are distributed which cannot be differentiated from the appearance. Loading dose of trial (1g of tranexamic acid in 10ml) or placebo (10 ml of sodium chloride 0.9%) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial or placebo mixed in 500ml sodium chloride 0.9% is given over 8 hours | Drug: Tranexamic Acid 500 MG<br>* Loading dose of trial (1g of tranexamic acid in 10ml) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial mixed in 500ml sodium chloride 0.9% is given over 8 hours<br>|
| Placebo Comparator: Sodium Chloride<br>Four 5ml solution of either tranexamic acid 500mg or sodium chloride 0.9% are distributed which cannot be differentiated from the appearance. Loading dose of trial (1g of tranexamic acid in 10ml) or placebo (10 ml of sodium chloride 0.9%) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial or placebo mixed in 500ml sodium chloride 0.9% is given over 8 hours | Drug: Tranexamic Acid 500 MG<br>* Loading dose of trial (1g of tranexamic acid in 10ml) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial mixed in 500ml sodium chloride 0.9% is given over 8 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological improvement (CT scan) | Difference between hematoma volume from baseline and 48-hour post treatment scan | 48 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale | Neurological impairment (score:0-42; 0:favourable outcome) | day 7 | 
| Barthel index | Disability (score:0-100; 100: independent) | days 10 and 90, 180 | 
| modified rankin scale | dependency (score:0-5; 0: no symptom) | days 10 and 90, 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double blind randomized trial, spontaneous intracerebral hemorrhage, tranexamic acid