STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units
- Conditions
- Intracerebral Haemorrhage
- Interventions
- Drug: Normal saline
- Registration Number
- NCT03385928
- Lead Sponsor
- Neuroscience Trials Australia
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 201
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Saline (0.9% NaCl) Normal saline 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. Tranexamic acid Tranexamic Acid 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.
- Primary Outcome Measures
Name Time Method Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls) 24 hours(plus or minus 6 hours) Relative ICH haematoma growth
- Secondary Outcome Measures
Name Time Method Relative haematoma growth by 24±6 hours 24 hour ±6 hours Relative ICH growth volume, adjusted for baseline ICH volume
Absolute haematoma growth by 24±6 hours 24 hours ±6 hours ICH growth as defined by either ≥33%or ≥6ml increase from baseline from baseline, adjusted for baseline ICH volume
Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours 24 hours ±6 hours ICH plus IVH growth from baseline
The number of patients with mRS 0-4 or back to pre-stroke level at 3 months 90 days ± 7 days mRS 0-4 or back to pre-stroke level at 3 months
Death within 3 months 3 months from baseline Safety outcome
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 24 hours ±6 hours ICH or IVH growth at 24 hours ±6 hours from baseline
Absolute intraventricular haematoma growth by 24 hours ±6 hours 24 hours ±6 hours IVH growth at 24 hours ±6 hours from baseline
Death within 7 days 7 days from baseline Safety outcome
Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months 3 months from baseline Safety outcome
The number of patients with mRS 0-3 or back to pre-stroke level at 3 months 90 days ± 7 days mRS 0-3 or back to pre-stroke level at 3 months
Categorical shift in mRS at 3 months 90 days ± 7 days 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)
Trial Locations
- Locations (25)
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Palmerston North Hospital
🇳🇿Palmerston North, New Zealand
Mobile Stroke Unit
🇦🇺Parkville, Victoria, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Helsinki University Hospital
🇫🇮Helsinki, Finland
E-DA Hospital
🇨🇳Kaohsiung City, Yanchao District, Taiwan
CDHB Christchurch Hospital
🇳🇿Christchurch, New Zealand
Wellington Hospital
🇳🇿Wellington, New Zealand
China Medical University Hospital
🇨🇳Taichung City, Taiwan
Bach Mai Hospital
🇻🇳Hanoi, Vietnam
Military 103 Hospital
🇻🇳Hanoi, Vietnam
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
John Hunter Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Nguyen Tri Phuong Hospital
🇻🇳Ho Chi Minh City, Vietnam