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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
201
Investigational product given within 2 hours of symptom onset
Placebo given within 2 hours of symptom onset
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Haematoma growth by 24±6 hours as defined by either ≥33%or ≥6ml increase from baseline ICH volume (mls)
Relative ICH haematoma growth
Time frame: 24 hours(plus or minus 6 hours)
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
Time frame: 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
Time frame: 24 hours ±6 hours
Relative haematoma growth by 24±6 hours
Relative ICH growth volume, adjusted for baseline ICH volume
Time frame: 24 hour ±6 hours
Absolute intraventricular haematoma growth by 24 hours ±6 hours
IVH growth at 24 hours ±6 hours from baseline
Time frame: 24 hours ±6 hours
Absolute intracerebral plus intraventricular haematoma growth by 24±6 hours
ICH plus IVH growth from baseline
Time frame: 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
Time frame: 90 days ± 7 days
The number of patients with mRS 0-4 or back to pre-stroke level at 3 months
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Liverpool, New South Wales, Australia
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Southport, Queensland, Australia
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Box Hill, Victoria, Australia
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mRS 0-4 or back to pre-stroke level at 3 months
Time frame: 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)
Time frame: 90 days ± 7 days
Major thromboembolic events (myocardial infarction, ischaemic stroke, or pulmonary embolism) within 3 months
Safety outcome
Time frame: 3 months from baseline
Death within 3 months
Safety outcome
Time frame: 3 months from baseline
Death within 7 days
Safety outcome
Time frame: 7 days from baseline