STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units

Study Overview
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Brief Summary
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The study is a prospective phase II randomised, double-blind, placebo-controlled investigator-driven trial in acute intracerebral haemorrhage patients. The study has 2 arms with 1:1 randomisation to either intravenous tranexamic acid or placebo and will test the hypothesis that in patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared to placebo.

Detailed Description
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The trial will include patients with acute spontaneous ICH, who are ≥18 years of age and are eligible for treatment within 2 hours of stroke onset. A sample size of 326 patients is calculated to give 80% power to detect a large effect size assuming mean relative ICH haematoma growth of 38% in the placebo arm compared to 19% in the active treatment arm and standard deviation of 19%, inflated for nonparametric analysis. Adaptive increase in sample size will be performed if the result of interim analysis of the first 144 patients is promising, using the methodology of Mehta and Pocock. The maximum sample size is capped at 326. Standard CT for initial diagnosis of suspected stroke patients will be performed. Neurological impairment and functional scores will be measured by a neurologist or health care professional trained in their administration. The assessors will be blinded to the treatment group. Patients eligible for the RCT will be randomised in a 1:1 ratio to receive either tranexamic acid or placebo stratified by treating centre and utilising randomly permuted blocks of random size.

Official Title
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STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units. A Phase II Randomised, Placebo-controlled, Investigator-driven Trial of Tranexamic Acid Within 2 Hours of Intracerebral Haemorrhage

Conditions
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Intracerebral Haemorrhage

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with an acute ICH Age ≥18 years Treatment can commence within 2 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well) Consent can be obtained from participant or person responsible. When emergency treatment procedures have been followed the participant or person responsible will be asked for consent to continue in the study. 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, tumour, or infection 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 72 hours. 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.

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
Interventional Model Description: The study is a prospective phase II randomised, double-blind, placebo-controlled, investigator-driven trial in acute intracerebral haemorrhage patients. The study has 2 arms with 1:1 randomisation to either intravenous tranexamic acid or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic acid<br>Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl (or in 50ml syringe with 0.9% NaCl) over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours. | Drug: Tranexamic Acid<br>* Investigational product given within 2 hours of symptom onset<br>|
| Placebo Comparator: Normal Saline (0.9% NaCl)<br>100 mls (or in 50ml syringe) intravenous 0.9%NaCl over 10 minutes followed by 500 ml intravenous 0.9% NaCl infusion over 8 hours. | Drug: Normal saline<br>* Placebo given within 2 hours of symptom onset<br>* Other names: 0.9%NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls) | Relative ICH haematoma growth | 24 hours(plus or minus 6 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematoma growth by 24±6 hours as defined by ≥33%or ≥6ml increase from baseline in intracerebral haematoma volume, or any increase intraventricular haematoma volume | ICH or IVH growth at 24 hours ±6 hours from baseline | 24 hours ±6 hours | 
| Absolute haematoma growth by 24±6 hours | ICH growth as defined by either ≥33%or ≥6ml increase from baseline from baseline, adjusted for baseline ICH volume | 24 hours ±6 hours | 
| Relative haematoma growth by 24±6 hours | Relative ICH growth volume, adjusted for baseline ICH volume | 24 hour ±6 hours | 
| Absolute intraventricular haematoma growth by 24 hours ±6 hours | IVH growth at 24 hours ±6 hours from baseline | 24 hours ±6 hours | 
| Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours | ICH plus IVH growth from baseline | 24 hours ±6 hours | 
| The number of patients with mRS 0-3 or back to pre-stroke level at 3 months | mRS 0-3 or back to pre-stroke level at 3 months | 90 days ± 7 days | 
| The number of patients with mRS 0-4 or back to pre-stroke level at 3 months | mRS 0-4 or back to pre-stroke level at 3 months | 90 days ± 7 days | 
| Categorical shift in mRS at 3 months | mRS 0-4 or back to pre-stroke level, or mRS 0-3 or back to pre-stroke level (with lowest mRS score being the better outcome) | 90 days ± 7 days | 
| Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months | Safety outcome | 3 months from baseline | 
| Death within 3 months | Safety outcome | 3 months from baseline | 
| Death within 7 days | Safety outcome | 7 days from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICH, Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Tranexamic Acid, Antifibrinolytic Agents, Fibrin Modulating Agents, Pharmacologic Actions, Cardiovascular Agents, Therapeutic Uses, Hematologic Agents, Hemostatics, Contrast Media, Angiography, Cerebral Angiography, Tomography, X-Ray Computed