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

Neuroscience Trials Australia

Status and phase: Completed; Phase 2

Conditions: Intracerebral Haemorrhage

Treatments: Drug: Tranexamic Acid; Drug: Normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03385928

NTA1702

Details and patient eligibility

About

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.

Full 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.

Enrollment: 201 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients presenting with an acute ICH
2. Age ≥18 years
3. 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)
4. 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

1. Glasgow coma scale (GCS) total score of <8
2. Brainstem ICH
3. ICH volume >70 ml as measured by the ABC/2 method
4. 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
5. 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.
6. Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency.
7. 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.
8. Pregnancy (women of childbearing potential must be tested)
9. Planned surgery for ICH within 24 hours
10. Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion)
11. Participation in any investigational study in the last 30 days
12. Known terminal illness or planned withdrawal of care or comfort care measures
13. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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201 participants in 2 patient groups, including a placebo group

Tranexamic acid

Active Comparator group

Description:

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.

Treatment:

Drug: Tranexamic Acid

Normal Saline (0.9% NaCl)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Normal saline